Hye-Joo Kwon - Academia.edu (original) (raw)

Papers by Hye-Joo Kwon

Developmental Biology, Mar 1, 2018

Formation of neural and sensory progenitors in the inner ear requires Sox2 in mammals, and in oth... more Formation of neural and sensory progenitors in the inner ear requires Sox2 in mammals, and in other species is thought to rely on both Sox2 and Sox3. How Sox2 and/or Sox3 promote different fates is poorly understood. Our mutant analysis in zebrafish showed that sox2 is uniquely required for sensory development while sox3 is uniquely required for neurogenesis. Moderate misexpression of sox2 during placodal stages led to development of otic vesicles with expanded sensory and reduced neurogenic domains. However, high-level misexpression of sox2 or sox3 expanded both sensory and neurogenic domains to fill the medial and lateral halves of the otic vesicle, respectively. Disruption of medial factor pax2a eliminated the ability of sox2/3 misexpression to expand sensory but not neurogenic domains. Additionally, mild misexpression of fgf8 during placodal development was sufficient to specifically expand the zone of prosensory competence. Later, cross-repression between atohla and neurogl helps maintain the sensory-neural boundary, but unlike mouse this does not require Notch activity. Together, these data show that sox2 and sox3 exhibit intrinsic differences in promoting sensory vs. neural competence, but at high levels these factors can mimic each other to enhance both states. Regional cofactors like pax2a and fgf8 also modify sox2/3 functions.

Developmental Biology, 2013

Preplacodal ectoderm (PPE) and neural crest (NC) are specified at the interface of neural and non... more Preplacodal ectoderm (PPE) and neural crest (NC) are specified at the interface of neural and nonneural ectoderm and together contribute to the peripheral nervous system in all vertebrates. Bmp activates early steps for both fates during late blastula stage. Low Bmp activates expression of transcription factors Tfap2a and Tfap2c in the lateral neural plate, thereby specifying neural crest fate. Elevated Bmp establishes preplacodal competence throughout the ventral ectoderm by coinducing Tfap2a, Tfap2c, Foxi1 and Gata3. PPE specification occurs later at the end of gastrulation and requires complete attenuation of Bmp, yet expression of PPE competence factors continues well past gastrulation. Here we show that competence factors positively regulate each other's expression during gastrulation, forming a self-sustaining network that operates independently of Bmp. Misexpression of Tfap2a in embryos blocked for Bmp from late blastula stage can restore development of both PPE and NC. However, Tfap2a alone is not sufficient to activate any other competence factors nor does it rescue individual placodes. On the other hand, misexpression of any two competence factors in Bmp-blocked embryos can activate the entire transcription factor network and support the development of NC, PPE and some individual placodes. We also show that while these factors are partially redundant with respect to PPE specification, they later provide non-redundant functions needed for development of specific placodes. Thus, we have identified a gene regulatory network that coordinates development of NC, PPE and individual placodes in zebrafish.

Biochemical and Biophysical Research Communications, Sep 1, 2016

The biological actions of vitamin D are largely mediated through binding to the vitamin D recepto... more The biological actions of vitamin D are largely mediated through binding to the vitamin D receptor (VDR), a member of the nuclear hormone receptor family, which regulates gene expression in a wide variety of tissues and cells. Mutations in VDR gene have been implicated in ear disorders (hearing loss and balance disorder) but the mechanisms are not well established. In this study, to investigate the role of VDR in inner ear development, morpholino-mediated gene knockdown approaches were used in zebrafish model system. Two paralogs for VDR, vdra and vdrb, have been identified in zebrafish. Knockdown of vdra had no effect on ear development, whereas knockdown of vdrb displayed morphological ear defects including smaller otic vesicles with malformed semicircular canals and abnormal otoliths. Loss-of-vdrb resulted in down-regulation of pre-otic markers, pax8 and pax2a, indicating impairment of otic induction. Furthermore, zebrafish embryos lacking vdrb produced fewer sensory hair cells in the ears and showed disruption of balance and motor coordination. These data reveal that VDR signaling plays an important role in ear development.

Developmental Biology, Jun 1, 2006

The zebrafish muscle segment homeobox genes msxB, msxC and msxE are expressed in partially overla... more The zebrafish muscle segment homeobox genes msxB, msxC and msxE are expressed in partially overlapping domains in the neural crest and preplacodal ectoderm. We examined the roles of these msx genes in early development. Disrupting individual msx genes causes modest variable defects, whereas disrupting all three produces a reproducible severe phenotype, suggesting functional redundancy. Neural crest differentiation is blocked at an early stage. Preplacodal development begins normally, but placodes arising from the msx expression domain later show elevated apoptosis and are reduced in size. Cell proliferation is normal in these tissues. Unexpectedly, Msx-deficient embryos become ventralized by late gastrulation whereas misexpression of msxB dorsalizes the embryo. These effects appear to involve Distal-less (Dlx) protein activity, as loss of dlx3b and dlx4b suppresses ventralization in Msx-depleted embryos. At the same time, Msx-depletion restores normal preplacodal gene expression to dlx3b-dlx4b mutants. These data suggest that mutual antagonism between Msx and Dlx proteins achieves a balance of function required for normal preplacodal differentiation and placement of the neural-nonneural border.

Our study shows that females had much higher IgG and IgM compared to age-matching males. A signif... more Our study shows that females had much higher IgG and IgM compared to age-matching males. A significant correlation between both antibodies and liver enzymes (AST, ALT) was recorded. Less significant correlation of both IgG and IgM with GGT was also observed. Receiver operating characteristics (ROC) analysis revealed that both IgG and IgM can be used as excellent predictive markers for CMV infection as both recorded 100% specificity and sensitivity together with area under the curve of 1 in males and females. Multiple regression analysis ascertain the correlation between both antibodies as dependent variables and liver enzymes as independent variables with ALT being the most affected enzyme with CMV seropositivity especially in females.This study shows that CMV is capable of initiating and accelerating liver dysfunction in both sexes. The high seroprevalence in females at reproductive age is especially important as they can transmit the virus to their developing fetus. Prevention of CMV infection in young girls 11-14 years old; the prevalence of congenital CMV infections may decreased by possible future vaccination and control on the most non-hepatorophic agent which developing liver dysfunction.

Development Genes and Evolution, Apr 27, 2001

We have isolated the Xenopus homologue of the receptor for activated C-kinase 1 (RACK1), whose am... more We have isolated the Xenopus homologue of the receptor for activated C-kinase 1 (RACK1), whose amino acid sequence shows significant similarity with other vertebrate RACK1s. XRACK1 is a maternally expressed gene and its zygotic expression is detected in the antero-dorsal region and dorsal midline in the late neurula. At tailbud stage, rather diffuse staining is seen in the somite and head. Later, XRACK1 mRNA is expressed highly in ventrally migrating abdominal muscle anlagen, where it remains expressed during subsequent stages.

Physiology & Behavior, 2020

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Journal of developmental biology, Jun 22, 2019

Vitamin D plays essential roles in supporting the skeletal system. The active form of vitamin D f... more Vitamin D plays essential roles in supporting the skeletal system. The active form of vitamin D functions through the vitamin D receptor (VDR). A hereditary vitamin-D-resistant rickets with facial dysmorphism has been reported, but the involvement of VDR signaling during early stages of craniofacial development remains to be elucidated. The present study investigated whether VDR signaling is implicated in zebrafish craniofacial cartilage development using a morpholino-based knockdown approach. Two paralogous VDR genes, vdra and vdrb, have been found in zebrafish embryos. Loss-of-vdra has no discernible effect on cartilage elements, whereas loss-of-vdrb causes reduction and malformation of craniofacial cartilages. Disrupting both vdra and vdrb leads to more severe defects or complete loss of cartilage. Notably, knockdown of vdrb results in elevated expression of follistatin a (fsta), a bone morphogenetic protein (BMP) antagonist, in the adjacent pharyngeal endoderm. Taken together, these findings strongly indicate that VDR signaling is required for early craniofacial cartilage development in zebrafish.

Biochemical and Biophysical Research Communications, 2016

Vitamin D has been found to be associated with cardiovascular diseases. However, the role of vita... more Vitamin D has been found to be associated with cardiovascular diseases. However, the role of vitamin D in heart development during embryonic period is largely unknown. Vitamin D induces its genomic effects through its nuclear receptor, the vitamin D receptor (VDR). The present study investigated the role of VDR on heart development by antisense-mediated knockdown approaches in zebrafish model system. In zebrafish embryos, two distinct VDR genes (vdra and vdrb) have been identified. Knockdown of vdra has little effect on heart development, whereas disrupting vdrb gene causes various cardiac phenotypes, characterized by pericardial edema, slower heart rate and laterality defects. Depletion of both vdra and vdrb (vdra/b) produce additive, but not synergistic effects. To determine whether atrioventricular (AV) cardiomyocytes are properly organized in these embryos, the expression of bmp4, which marks the developing AV boundary at 48 h post-fertilization, was examined. Notably, vdra/b-deficient embryos display ectopic expression of bmp4 towards the ventricle or throughout atrial and ventricular chambers. Taken together, these results suggest that VDR signaling plays an essential role in heart development.

Biochemical and Biophysical Research Communications, 2003

Polycomb group (PcG) genes are required for the stable repression of the homeotic genes and other... more Polycomb group (PcG) genes are required for the stable repression of the homeotic genes and other developmentally regulated genes. Yin Yang 1 (YY1), a vertebrate homolog of the Drosophila PcG pleiohomeotic (Pho), is a multifunctional protein that can act as a repressor or activator of transcription. Xenopus YY1 (XYY1) protein was localized in the central nervous system (CNS), particularly anterior neural tube of tailbud stage embryos. To elucidate the role of endogenous XYY1, loss-of-function studies were performed using XYY1 antisense morpholino oligonucleotide (XYY1 MO). Inhibition of XYY1 function resulted in embryos with antero-posterior axial patterning defects and reduction of head structures. XYY1 MO also reduced the expression of En2, a midbrain/hindbrain junction marker, which was rescued by co-injection of XYY1 mRNA. However, XYY1 MO-injection did not affect the expression of HoxB9, a spinal cord marker. These results suggest that YY1 controls antero-posterior patterning of the CNS during Xenopus embryonic development.

We have isolated the Xenopus homologue of the receptor for activated C-kinase 1 (RACK1), whose am... more We have isolated the Xenopus homologue of the receptor for activated C-kinase 1 (RACK1), whose amino acid sequence shows significant similarity with other vertebrate RACK1s. XRACK1 is a maternally expressed gene and its zygotic expression is detected in the antero-dorsal region and dorsal midline in the late neurula. At tailbud stage, rather diffuse staining is seen in the somite and head. Later, XRACK1 mRNA is expressed highly in ventrally migrating abdominal muscle anlagen, where it remains expressed during subsequent stages.

Experimental Results, 2021

Vitamin D is a steroid hormone well-known for its role in calcium homeostasis and bone health. Bi... more Vitamin D is a steroid hormone well-known for its role in calcium homeostasis and bone health. Biological actions of vitamin D are mediated through the vitamin D receptor (VDR) present in various cells and tissues. Vitamin D has been implicated in multiple aspects of neuromuscular functions. This study aimed to investigate the role of VDR signaling during early stage of locomotor development utilizing a gene knockdown approach. Zebrafish larvae deficient in VDR showed severe motor impairment and no obvious response to touch. These results indicate that VDR signaling is indispensable for the correct neuromuscular development and touch-evoked escape swimming behavior in zebrafish.

Journal of Developmental Biology, 2019

Vitamin D plays essential roles in supporting the skeletal system. The active form of vitamin D f... more Vitamin D plays essential roles in supporting the skeletal system. The active form of vitamin D functions through the vitamin D receptor (VDR). A hereditary vitamin-D-resistant rickets with facial dysmorphism has been reported, but the involvement of VDR signaling during early stages of craniofacial development remains to be elucidated. The present study investigated whether VDR signaling is implicated in zebrafish craniofacial cartilage development using a morpholino-based knockdown approach. Two paralogous VDR genes, vdra and vdrb, have been found in zebrafish embryos. Loss-of-vdra has no discernible effect on cartilage elements, whereas loss-of-vdrb causes reduction and malformation of craniofacial cartilages. Disrupting both vdra and vdrb leads to more severe defects or complete loss of cartilage. Notably, knockdown of vdrb results in elevated expression of follistatin a (fsta), a bone morphogenetic protein (BMP) antagonist, in the adjacent pharyngeal endoderm. Taken together, t...

Biochemical and Biophysical Research Communications, 2016

The biological actions of vitamin D are largely mediated through binding to the vitamin D recepto... more The biological actions of vitamin D are largely mediated through binding to the vitamin D receptor (VDR), a member of the nuclear hormone receptor family, which regulates gene expression in a wide variety of tissues and cells. Mutations in VDR gene have been implicated in ear disorders (hearing loss and balance disorder) but the mechanisms are not well established. In this study, to investigate the role of VDR in inner ear development, morpholino-mediated gene knockdown approaches were used in zebrafish model system. Two paralogs for VDR, vdra and vdrb, have been identified in zebrafish. Knockdown of vdra had no effect on ear development, whereas knockdown of vdrb displayed morphological ear defects including smaller otic vesicles with malformed semicircular canals and abnormal otoliths. Loss-of-vdrb resulted in down-regulation of pre-otic markers, pax8 and pax2a, indicating impairment of otic induction. Furthermore, zebrafish embryos lacking vdrb produced fewer sensory hair cells in the ears and showed disruption of balance and motor coordination. These data reveal that VDR signaling plays an important role in ear development.

Experimental Neurobiology, 2012

Depression is a prevailing form of psychiatric illness worldwide, but the underlying mechanism is... more Depression is a prevailing form of psychiatric illness worldwide, but the underlying mechanism is not clearly elaborated. Recent progresses in the establishment of depression animal models give us a hope to unravel the molecular mechanism of depression and to develop advanced anti-depression strategies [1, 2]. Mice or rats exposed to a variety of stressors over a prolonged period display behavioral changes that parallel depression-like symptoms, such as decreased social interaction, decreased intake of sucrose, increased immobility time in helpless conditions such as in the forced swim test and tail suspension test [3-5]. Th ese stress-induced behavioral changes are generally reversed by chronic, but not acute, treatment with antidepressant drugs, such as imipramine or fluoxetine [4, 6], supporting the usefulness of stress-induced animal models in depression studies. Regarding animals models, various stressors are delivered repeatedly or continuously in mice or rats for a certain period of time to recapitulate depression pathophysiology in human. Among

Journal of Pure and Applied Microbiology, 2018

Princess nourah bint abdulrahman university (Pnu), Kingdom of Saudi arabia (KSa). 2 Prof of genet... more Princess nourah bint abdulrahman university (Pnu), Kingdom of Saudi arabia (KSa). 2 Prof of genetic, biology department, Princess nourah bint abdulrahman university (Pnu), Kingdom of Saudi arabia (KSa).

Asian Pacific Journal of Cancer Prevention, 2019

Background: Due to the prevalence of Hepatocellular carcinoma (HCC) in Saudi Arabia, using new ma... more Background: Due to the prevalence of Hepatocellular carcinoma (HCC) in Saudi Arabia, using new markers to give best diagnostic performance than alpha-feto protein (AFP) are important in early diagnosis. The aim of this work was to compare the significance between serum and mRNA Golgi glypican73 (GP-73) as newly identified diagnostic and prognostic markers for HCC among Saudi patients. Materials and Methods: A total of 300 subjects were divided into: 250 blood samples where 145 samples from HCC, 105 samples from chronic liver cirrhosis (CLC) and 50 normal controls were investigated for serum GP73 (sGP73) by ELISA. GP-73 mRNA from peripheral blood mononuclear cells was amplified by RT-PCR. The sensitivity and specificity of both techniques was compared. Results: Serum Golgi glypican 73 was significantly higher in HCC group compared to cirrhotic and normal controls (p<0.001). Sensitivity and specificity were 95% for sGP-73, 100% and 90% for Golgi glypican 73 mRNA. The combination of sensitivity between AFP and sGP73 was 80% and 95% respectively. Conclusion: Both serum Golgi glypican-73 and GP-73Mrna are good diagnostic biomarkers for early detection of HCC in Saudi patients. RT-PCR is more accurate and sensitive (100%) than ELISA (95%) in detecting Golgi glypican 73.

Biomedical and Pharmacology Journal, 2018

In Saudi Arabia AFP considered the main serum marker for diagnostic Hepatocellular carcinoma (HCC... more In Saudi Arabia AFP considered the main serum marker for diagnostic Hepatocellular carcinoma (HCC), due to the continuous detection of HCC in Saudi Arabia, using new biomarkers for early surveillance are essential to control in prevalence of HCC. The present study depend on compare the significant between serum and mRNA Glypican-3 (GPC-3) as newly identified diagnostic and prognostic biomarkers for HCC between study cases. And combined sensitivity of AFP and GPC-3. Three hundred study cases, divided into: 250 blood samples were 145 samples from HCC , 105 samples from chronic liver cirrhosis (CLC) and 50 normal controls were investigated for serum GPC-3 (sGPC-3) by Sandwich ELISA. Glypican-3 mRNA from whole blood cells was detected by quantitative RT-PCR. The comparison between two techniques was by sensitivity and specificity. The results of sGPC-3 showed higher significant in HCC group than CLC and normal controls (p<0.001). sGPC-3 sensitivity was 95% and specificity was 100%, w...

Developmental Biology, 2018

Formation of neural and sensory progenitors in the inner ear requires Sox2 in mammals, and in oth... more Formation of neural and sensory progenitors in the inner ear requires Sox2 in mammals, and in other species is thought to rely on both Sox2 and Sox3. How Sox2 and/or Sox3 promote different fates is poorly understood. Our mutant analysis in zebrafish showed that sox2 is uniquely required for sensory development while sox3 is uniquely required for neurogenesis. Moderate misexpression of sox2 during placodal stages led to development of otic vesicles with expanded sensory and reduced neurogenic domains. However, high-level misexpression of sox2 or sox3 expanded both sensory and neurogenic domains to fill the medial and lateral halves of the otic vesicle, respectively. Disruption of medial factor pax2a eliminated the ability of sox2/3 misexpression to expand sensory but not neurogenic domains. Additionally, mild misexpression of fgf8 during placodal development was sufficient to specifically expand the zone of prosensory competence. Later, cross-repression between atohla and neurogl helps maintain the sensory-neural boundary, but unlike mouse this does not require Notch activity. Together, these data show that sox2 and sox3 exhibit intrinsic differences in promoting sensory vs. neural competence, but at high levels these factors can mimic each other to enhance both states. Regional cofactors like pax2a and fgf8 also modify sox2/3 functions.

Background: Exposure to chronic low levels of aflatoxin B1 (AFB1) contamination can lead to immun... more Background: Exposure to chronic low levels of aflatoxin B1 (AFB1) contamination can lead to immune suppression and nutritional consequences that might greatly contributed in the increase of hepatocellular carcinoma (HCC). The toxicity of AFB1 is greatly vary between different population, affected by age, gender, and environmental factors. Material and subjects: Aflatoxin B1 (AFB1) was measured in 50 blood samples collected from non B, C hepatitis viruses and non CMV-Ab liver disease patients from different general hospitals and polyclinic in KSA during period 01-2013 to 06-2014. All Patients demonstrate elevation of ALT and AST with unknown etiology. Serum samples were obtained and kept at −20 °C for AFB1detection. Results: Out of the 50 blood samples, 38 demonstrate a detectable serum level of AFB1 while the remaining 12 patients were AFB1 negative and used as control participants. While AST was non-significantly different in AFB1 exposed patients, ALT was significantly h...

Developmental Biology, Mar 1, 2018

Formation of neural and sensory progenitors in the inner ear requires Sox2 in mammals, and in oth... more Formation of neural and sensory progenitors in the inner ear requires Sox2 in mammals, and in other species is thought to rely on both Sox2 and Sox3. How Sox2 and/or Sox3 promote different fates is poorly understood. Our mutant analysis in zebrafish showed that sox2 is uniquely required for sensory development while sox3 is uniquely required for neurogenesis. Moderate misexpression of sox2 during placodal stages led to development of otic vesicles with expanded sensory and reduced neurogenic domains. However, high-level misexpression of sox2 or sox3 expanded both sensory and neurogenic domains to fill the medial and lateral halves of the otic vesicle, respectively. Disruption of medial factor pax2a eliminated the ability of sox2/3 misexpression to expand sensory but not neurogenic domains. Additionally, mild misexpression of fgf8 during placodal development was sufficient to specifically expand the zone of prosensory competence. Later, cross-repression between atohla and neurogl helps maintain the sensory-neural boundary, but unlike mouse this does not require Notch activity. Together, these data show that sox2 and sox3 exhibit intrinsic differences in promoting sensory vs. neural competence, but at high levels these factors can mimic each other to enhance both states. Regional cofactors like pax2a and fgf8 also modify sox2/3 functions.

Developmental Biology, 2013

Preplacodal ectoderm (PPE) and neural crest (NC) are specified at the interface of neural and non... more Preplacodal ectoderm (PPE) and neural crest (NC) are specified at the interface of neural and nonneural ectoderm and together contribute to the peripheral nervous system in all vertebrates. Bmp activates early steps for both fates during late blastula stage. Low Bmp activates expression of transcription factors Tfap2a and Tfap2c in the lateral neural plate, thereby specifying neural crest fate. Elevated Bmp establishes preplacodal competence throughout the ventral ectoderm by coinducing Tfap2a, Tfap2c, Foxi1 and Gata3. PPE specification occurs later at the end of gastrulation and requires complete attenuation of Bmp, yet expression of PPE competence factors continues well past gastrulation. Here we show that competence factors positively regulate each other's expression during gastrulation, forming a self-sustaining network that operates independently of Bmp. Misexpression of Tfap2a in embryos blocked for Bmp from late blastula stage can restore development of both PPE and NC. However, Tfap2a alone is not sufficient to activate any other competence factors nor does it rescue individual placodes. On the other hand, misexpression of any two competence factors in Bmp-blocked embryos can activate the entire transcription factor network and support the development of NC, PPE and some individual placodes. We also show that while these factors are partially redundant with respect to PPE specification, they later provide non-redundant functions needed for development of specific placodes. Thus, we have identified a gene regulatory network that coordinates development of NC, PPE and individual placodes in zebrafish.

Biochemical and Biophysical Research Communications, Sep 1, 2016

The biological actions of vitamin D are largely mediated through binding to the vitamin D recepto... more The biological actions of vitamin D are largely mediated through binding to the vitamin D receptor (VDR), a member of the nuclear hormone receptor family, which regulates gene expression in a wide variety of tissues and cells. Mutations in VDR gene have been implicated in ear disorders (hearing loss and balance disorder) but the mechanisms are not well established. In this study, to investigate the role of VDR in inner ear development, morpholino-mediated gene knockdown approaches were used in zebrafish model system. Two paralogs for VDR, vdra and vdrb, have been identified in zebrafish. Knockdown of vdra had no effect on ear development, whereas knockdown of vdrb displayed morphological ear defects including smaller otic vesicles with malformed semicircular canals and abnormal otoliths. Loss-of-vdrb resulted in down-regulation of pre-otic markers, pax8 and pax2a, indicating impairment of otic induction. Furthermore, zebrafish embryos lacking vdrb produced fewer sensory hair cells in the ears and showed disruption of balance and motor coordination. These data reveal that VDR signaling plays an important role in ear development.

Developmental Biology, Jun 1, 2006

The zebrafish muscle segment homeobox genes msxB, msxC and msxE are expressed in partially overla... more The zebrafish muscle segment homeobox genes msxB, msxC and msxE are expressed in partially overlapping domains in the neural crest and preplacodal ectoderm. We examined the roles of these msx genes in early development. Disrupting individual msx genes causes modest variable defects, whereas disrupting all three produces a reproducible severe phenotype, suggesting functional redundancy. Neural crest differentiation is blocked at an early stage. Preplacodal development begins normally, but placodes arising from the msx expression domain later show elevated apoptosis and are reduced in size. Cell proliferation is normal in these tissues. Unexpectedly, Msx-deficient embryos become ventralized by late gastrulation whereas misexpression of msxB dorsalizes the embryo. These effects appear to involve Distal-less (Dlx) protein activity, as loss of dlx3b and dlx4b suppresses ventralization in Msx-depleted embryos. At the same time, Msx-depletion restores normal preplacodal gene expression to dlx3b-dlx4b mutants. These data suggest that mutual antagonism between Msx and Dlx proteins achieves a balance of function required for normal preplacodal differentiation and placement of the neural-nonneural border.

Our study shows that females had much higher IgG and IgM compared to age-matching males. A signif... more Our study shows that females had much higher IgG and IgM compared to age-matching males. A significant correlation between both antibodies and liver enzymes (AST, ALT) was recorded. Less significant correlation of both IgG and IgM with GGT was also observed. Receiver operating characteristics (ROC) analysis revealed that both IgG and IgM can be used as excellent predictive markers for CMV infection as both recorded 100% specificity and sensitivity together with area under the curve of 1 in males and females. Multiple regression analysis ascertain the correlation between both antibodies as dependent variables and liver enzymes as independent variables with ALT being the most affected enzyme with CMV seropositivity especially in females.This study shows that CMV is capable of initiating and accelerating liver dysfunction in both sexes. The high seroprevalence in females at reproductive age is especially important as they can transmit the virus to their developing fetus. Prevention of CMV infection in young girls 11-14 years old; the prevalence of congenital CMV infections may decreased by possible future vaccination and control on the most non-hepatorophic agent which developing liver dysfunction.

Development Genes and Evolution, Apr 27, 2001

We have isolated the Xenopus homologue of the receptor for activated C-kinase 1 (RACK1), whose am... more We have isolated the Xenopus homologue of the receptor for activated C-kinase 1 (RACK1), whose amino acid sequence shows significant similarity with other vertebrate RACK1s. XRACK1 is a maternally expressed gene and its zygotic expression is detected in the antero-dorsal region and dorsal midline in the late neurula. At tailbud stage, rather diffuse staining is seen in the somite and head. Later, XRACK1 mRNA is expressed highly in ventrally migrating abdominal muscle anlagen, where it remains expressed during subsequent stages.

Physiology & Behavior, 2020

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Journal of developmental biology, Jun 22, 2019

Vitamin D plays essential roles in supporting the skeletal system. The active form of vitamin D f... more Vitamin D plays essential roles in supporting the skeletal system. The active form of vitamin D functions through the vitamin D receptor (VDR). A hereditary vitamin-D-resistant rickets with facial dysmorphism has been reported, but the involvement of VDR signaling during early stages of craniofacial development remains to be elucidated. The present study investigated whether VDR signaling is implicated in zebrafish craniofacial cartilage development using a morpholino-based knockdown approach. Two paralogous VDR genes, vdra and vdrb, have been found in zebrafish embryos. Loss-of-vdra has no discernible effect on cartilage elements, whereas loss-of-vdrb causes reduction and malformation of craniofacial cartilages. Disrupting both vdra and vdrb leads to more severe defects or complete loss of cartilage. Notably, knockdown of vdrb results in elevated expression of follistatin a (fsta), a bone morphogenetic protein (BMP) antagonist, in the adjacent pharyngeal endoderm. Taken together, these findings strongly indicate that VDR signaling is required for early craniofacial cartilage development in zebrafish.

Biochemical and Biophysical Research Communications, 2016

Vitamin D has been found to be associated with cardiovascular diseases. However, the role of vita... more Vitamin D has been found to be associated with cardiovascular diseases. However, the role of vitamin D in heart development during embryonic period is largely unknown. Vitamin D induces its genomic effects through its nuclear receptor, the vitamin D receptor (VDR). The present study investigated the role of VDR on heart development by antisense-mediated knockdown approaches in zebrafish model system. In zebrafish embryos, two distinct VDR genes (vdra and vdrb) have been identified. Knockdown of vdra has little effect on heart development, whereas disrupting vdrb gene causes various cardiac phenotypes, characterized by pericardial edema, slower heart rate and laterality defects. Depletion of both vdra and vdrb (vdra/b) produce additive, but not synergistic effects. To determine whether atrioventricular (AV) cardiomyocytes are properly organized in these embryos, the expression of bmp4, which marks the developing AV boundary at 48 h post-fertilization, was examined. Notably, vdra/b-deficient embryos display ectopic expression of bmp4 towards the ventricle or throughout atrial and ventricular chambers. Taken together, these results suggest that VDR signaling plays an essential role in heart development.

Biochemical and Biophysical Research Communications, 2003

Polycomb group (PcG) genes are required for the stable repression of the homeotic genes and other... more Polycomb group (PcG) genes are required for the stable repression of the homeotic genes and other developmentally regulated genes. Yin Yang 1 (YY1), a vertebrate homolog of the Drosophila PcG pleiohomeotic (Pho), is a multifunctional protein that can act as a repressor or activator of transcription. Xenopus YY1 (XYY1) protein was localized in the central nervous system (CNS), particularly anterior neural tube of tailbud stage embryos. To elucidate the role of endogenous XYY1, loss-of-function studies were performed using XYY1 antisense morpholino oligonucleotide (XYY1 MO). Inhibition of XYY1 function resulted in embryos with antero-posterior axial patterning defects and reduction of head structures. XYY1 MO also reduced the expression of En2, a midbrain/hindbrain junction marker, which was rescued by co-injection of XYY1 mRNA. However, XYY1 MO-injection did not affect the expression of HoxB9, a spinal cord marker. These results suggest that YY1 controls antero-posterior patterning of the CNS during Xenopus embryonic development.

We have isolated the Xenopus homologue of the receptor for activated C-kinase 1 (RACK1), whose am... more We have isolated the Xenopus homologue of the receptor for activated C-kinase 1 (RACK1), whose amino acid sequence shows significant similarity with other vertebrate RACK1s. XRACK1 is a maternally expressed gene and its zygotic expression is detected in the antero-dorsal region and dorsal midline in the late neurula. At tailbud stage, rather diffuse staining is seen in the somite and head. Later, XRACK1 mRNA is expressed highly in ventrally migrating abdominal muscle anlagen, where it remains expressed during subsequent stages.

Experimental Results, 2021

Vitamin D is a steroid hormone well-known for its role in calcium homeostasis and bone health. Bi... more Vitamin D is a steroid hormone well-known for its role in calcium homeostasis and bone health. Biological actions of vitamin D are mediated through the vitamin D receptor (VDR) present in various cells and tissues. Vitamin D has been implicated in multiple aspects of neuromuscular functions. This study aimed to investigate the role of VDR signaling during early stage of locomotor development utilizing a gene knockdown approach. Zebrafish larvae deficient in VDR showed severe motor impairment and no obvious response to touch. These results indicate that VDR signaling is indispensable for the correct neuromuscular development and touch-evoked escape swimming behavior in zebrafish.

Journal of Developmental Biology, 2019

Vitamin D plays essential roles in supporting the skeletal system. The active form of vitamin D f... more Vitamin D plays essential roles in supporting the skeletal system. The active form of vitamin D functions through the vitamin D receptor (VDR). A hereditary vitamin-D-resistant rickets with facial dysmorphism has been reported, but the involvement of VDR signaling during early stages of craniofacial development remains to be elucidated. The present study investigated whether VDR signaling is implicated in zebrafish craniofacial cartilage development using a morpholino-based knockdown approach. Two paralogous VDR genes, vdra and vdrb, have been found in zebrafish embryos. Loss-of-vdra has no discernible effect on cartilage elements, whereas loss-of-vdrb causes reduction and malformation of craniofacial cartilages. Disrupting both vdra and vdrb leads to more severe defects or complete loss of cartilage. Notably, knockdown of vdrb results in elevated expression of follistatin a (fsta), a bone morphogenetic protein (BMP) antagonist, in the adjacent pharyngeal endoderm. Taken together, t...

Biochemical and Biophysical Research Communications, 2016

The biological actions of vitamin D are largely mediated through binding to the vitamin D recepto... more The biological actions of vitamin D are largely mediated through binding to the vitamin D receptor (VDR), a member of the nuclear hormone receptor family, which regulates gene expression in a wide variety of tissues and cells. Mutations in VDR gene have been implicated in ear disorders (hearing loss and balance disorder) but the mechanisms are not well established. In this study, to investigate the role of VDR in inner ear development, morpholino-mediated gene knockdown approaches were used in zebrafish model system. Two paralogs for VDR, vdra and vdrb, have been identified in zebrafish. Knockdown of vdra had no effect on ear development, whereas knockdown of vdrb displayed morphological ear defects including smaller otic vesicles with malformed semicircular canals and abnormal otoliths. Loss-of-vdrb resulted in down-regulation of pre-otic markers, pax8 and pax2a, indicating impairment of otic induction. Furthermore, zebrafish embryos lacking vdrb produced fewer sensory hair cells in the ears and showed disruption of balance and motor coordination. These data reveal that VDR signaling plays an important role in ear development.

Experimental Neurobiology, 2012

Depression is a prevailing form of psychiatric illness worldwide, but the underlying mechanism is... more Depression is a prevailing form of psychiatric illness worldwide, but the underlying mechanism is not clearly elaborated. Recent progresses in the establishment of depression animal models give us a hope to unravel the molecular mechanism of depression and to develop advanced anti-depression strategies [1, 2]. Mice or rats exposed to a variety of stressors over a prolonged period display behavioral changes that parallel depression-like symptoms, such as decreased social interaction, decreased intake of sucrose, increased immobility time in helpless conditions such as in the forced swim test and tail suspension test [3-5]. Th ese stress-induced behavioral changes are generally reversed by chronic, but not acute, treatment with antidepressant drugs, such as imipramine or fluoxetine [4, 6], supporting the usefulness of stress-induced animal models in depression studies. Regarding animals models, various stressors are delivered repeatedly or continuously in mice or rats for a certain period of time to recapitulate depression pathophysiology in human. Among

Journal of Pure and Applied Microbiology, 2018

Princess nourah bint abdulrahman university (Pnu), Kingdom of Saudi arabia (KSa). 2 Prof of genet... more Princess nourah bint abdulrahman university (Pnu), Kingdom of Saudi arabia (KSa). 2 Prof of genetic, biology department, Princess nourah bint abdulrahman university (Pnu), Kingdom of Saudi arabia (KSa).

Asian Pacific Journal of Cancer Prevention, 2019

Background: Due to the prevalence of Hepatocellular carcinoma (HCC) in Saudi Arabia, using new ma... more Background: Due to the prevalence of Hepatocellular carcinoma (HCC) in Saudi Arabia, using new markers to give best diagnostic performance than alpha-feto protein (AFP) are important in early diagnosis. The aim of this work was to compare the significance between serum and mRNA Golgi glypican73 (GP-73) as newly identified diagnostic and prognostic markers for HCC among Saudi patients. Materials and Methods: A total of 300 subjects were divided into: 250 blood samples where 145 samples from HCC, 105 samples from chronic liver cirrhosis (CLC) and 50 normal controls were investigated for serum GP73 (sGP73) by ELISA. GP-73 mRNA from peripheral blood mononuclear cells was amplified by RT-PCR. The sensitivity and specificity of both techniques was compared. Results: Serum Golgi glypican 73 was significantly higher in HCC group compared to cirrhotic and normal controls (p<0.001). Sensitivity and specificity were 95% for sGP-73, 100% and 90% for Golgi glypican 73 mRNA. The combination of sensitivity between AFP and sGP73 was 80% and 95% respectively. Conclusion: Both serum Golgi glypican-73 and GP-73Mrna are good diagnostic biomarkers for early detection of HCC in Saudi patients. RT-PCR is more accurate and sensitive (100%) than ELISA (95%) in detecting Golgi glypican 73.

Biomedical and Pharmacology Journal, 2018

In Saudi Arabia AFP considered the main serum marker for diagnostic Hepatocellular carcinoma (HCC... more In Saudi Arabia AFP considered the main serum marker for diagnostic Hepatocellular carcinoma (HCC), due to the continuous detection of HCC in Saudi Arabia, using new biomarkers for early surveillance are essential to control in prevalence of HCC. The present study depend on compare the significant between serum and mRNA Glypican-3 (GPC-3) as newly identified diagnostic and prognostic biomarkers for HCC between study cases. And combined sensitivity of AFP and GPC-3. Three hundred study cases, divided into: 250 blood samples were 145 samples from HCC , 105 samples from chronic liver cirrhosis (CLC) and 50 normal controls were investigated for serum GPC-3 (sGPC-3) by Sandwich ELISA. Glypican-3 mRNA from whole blood cells was detected by quantitative RT-PCR. The comparison between two techniques was by sensitivity and specificity. The results of sGPC-3 showed higher significant in HCC group than CLC and normal controls (p<0.001). sGPC-3 sensitivity was 95% and specificity was 100%, w...

Developmental Biology, 2018

Formation of neural and sensory progenitors in the inner ear requires Sox2 in mammals, and in oth... more Formation of neural and sensory progenitors in the inner ear requires Sox2 in mammals, and in other species is thought to rely on both Sox2 and Sox3. How Sox2 and/or Sox3 promote different fates is poorly understood. Our mutant analysis in zebrafish showed that sox2 is uniquely required for sensory development while sox3 is uniquely required for neurogenesis. Moderate misexpression of sox2 during placodal stages led to development of otic vesicles with expanded sensory and reduced neurogenic domains. However, high-level misexpression of sox2 or sox3 expanded both sensory and neurogenic domains to fill the medial and lateral halves of the otic vesicle, respectively. Disruption of medial factor pax2a eliminated the ability of sox2/3 misexpression to expand sensory but not neurogenic domains. Additionally, mild misexpression of fgf8 during placodal development was sufficient to specifically expand the zone of prosensory competence. Later, cross-repression between atohla and neurogl helps maintain the sensory-neural boundary, but unlike mouse this does not require Notch activity. Together, these data show that sox2 and sox3 exhibit intrinsic differences in promoting sensory vs. neural competence, but at high levels these factors can mimic each other to enhance both states. Regional cofactors like pax2a and fgf8 also modify sox2/3 functions.

Background: Exposure to chronic low levels of aflatoxin B1 (AFB1) contamination can lead to immun... more Background: Exposure to chronic low levels of aflatoxin B1 (AFB1) contamination can lead to immune suppression and nutritional consequences that might greatly contributed in the increase of hepatocellular carcinoma (HCC). The toxicity of AFB1 is greatly vary between different population, affected by age, gender, and environmental factors. Material and subjects: Aflatoxin B1 (AFB1) was measured in 50 blood samples collected from non B, C hepatitis viruses and non CMV-Ab liver disease patients from different general hospitals and polyclinic in KSA during period 01-2013 to 06-2014. All Patients demonstrate elevation of ALT and AST with unknown etiology. Serum samples were obtained and kept at −20 °C for AFB1detection. Results: Out of the 50 blood samples, 38 demonstrate a detectable serum level of AFB1 while the remaining 12 patients were AFB1 negative and used as control participants. While AST was non-significantly different in AFB1 exposed patients, ALT was significantly h...