Darrell Wiens | University of Northern Iowa (original) (raw)
Papers by Darrell Wiens
Microscopy and Microanalysis, Aug 1, 1997
Formation of the chick heart is initiated when paired regions of the mesoderm migrate to a specif... more Formation of the chick heart is initiated when paired regions of the mesoderm migrate to a specific region in the primitive head. Certain cells eventually form a pair of endocardiac tubes that become the lining of the heart, while the remaining precardiac mesoderm ultimately differentiates into the myocardium. Fibronectin is suspected as a crucial component of the migratory process. Very few investigations have been conducted on the relationship between cell motility and microgravity.The primary objectives of this investigation were to determine the effect of altered gravity on the production and distribution of fibronectin, an extracellular matrix glycoprotein, during embryonic development of the chick heart, and to ascertain the extent to which these alterations affect myogenesis or morphogenesis. A microgravity bioreactor vessel, originally designed by NASA as a low-shear culture system, was employed to culture the cellular expiants in a simulated microgravity environment. Fertile, White-Leghorn chicken eggs were incubated at 38°C for 32 hours in a humidified egg incubator.
Annals of Behavioral Neuroscience, 2019
Background: Valproic acid (VPA) is an anti-convulsant drug used to treat seizures and a variety o... more Background: Valproic acid (VPA) is an anti-convulsant drug used to treat seizures and a variety of neural pathologies. Studies have shown that VPA exposure in rodent embryos leads to behavioral characteristics similar to those in humans with autism spectrum disorder (ASD). Utilizing this rodent model of ASD, research has led to a recognized mechanism of action of VPA involving brain overgrowth and hyperconnectivity, likely caused by epigenetic alteration of gene expression through inhibition of histone deacetylases.Objective: To gain further insight concerning this mechanism we modeled the development of neural connectivity at the cellular level.Method: We cultured dorsal root ganglia (DRGs) taken from eight-day old chick embryos in a range of VPA concentrations and investigated aspects of neuronal structure and behavior. DRGs were cultured 48 hours, fixed, and immunostained to reveal the locations of neural networks with synaptic vesicles.Results: We found a concentration-dependant...
Cadherin-11 (cad-11) is primarily a mesenchymal cadherin that appears in delaminating neural cres... more Cadherin-11 (cad-11) is primarily a mesenchymal cadherin that appears in delaminating neural crest cells. Its expression correlates with morphogenetic events and the pattern has been studied in mouse, rat and Xenopus embryos, but not during avian organogenesis. Our purpose was to investigate this pattern in the chick embryo during organogenesis using immunolocalization and in situ hybridization. Cad-11 was expressed in mesenchyme around the pharynx and aortic arches, eyes, auditory vesicles, lung buds, stomach, and nasal placodes. Neural expression included some cranial ganglia and also new neuroepithelium within the tail bud region undergoing secondary neurulation. We also found expression in epithelia of the developing circulatory and digestive organs. The limb buds, pineal rudiment and mesonephros were also positive. Cad-11 expression became more widespread with development. Our findings support the role of cad-11 as a mesenchymal cadherin, but provide evidence for a wider role t...
All life on earth has developed and evolved in a unity gravity (1G) environment. Any deviation be... more All life on earth has developed and evolved in a unity gravity (1G) environment. Any deviation below or above 1G could affect animal development, a period when much change occurs and sensitivity is high. We imposed simulated hypergravity through centrifugation and analyzed the effects on the overall body length and cardiac growth of Xenopus laevis embryos. We predicted that increased contractile force would be required from the heart to adequately circulate blood, dispersing nutrients, and that this would inhibit organism growth and possibly induce a state of hypertrophy. Embryos reaching gastrulation stage were exposed to a 7G or 1G (control) field via centrifugation for 96 hours. We then recorded behavior, mortality and took body length measurements. We found no significant differences in behavior or mortality, however, body length was significantly reduced by an average of 6.8% in the 7G group. We then fixed, embedded, sectioned and stained embryos in order to investigate the dim...
The vitamin folic acid (FA) is essential for DNA synthesis, repair and methylation, and for methi... more The vitamin folic acid (FA) is essential for DNA synthesis, repair and methylation, and for methionine synthesis. Although it is necessary for neural development, recent studies suggest a possible link between excess maternal supplemental FA intake and adverse interferences with single-carbon metabolism and neural development. Insufficient FA early in brain development can lead to failure of the neural tube closure, but the consequences of too much intake have not been fully investigated. Plasma FA concentrations can increase greatly with dietary supplementation. To model the development of neural connectivity, we cultured dorsal root ganglia (DRGs) taken from 8-day-old chick embryos in a range of pteroylmonoglutamate (PteGlu, synthetic supplemental FA) concentrations. DRGs were cultured for 36 h, fixed and immunostained to reveal the locations of neural networks with synaptic vesicles. We found a concentration-dependent relationship with significant reduction in neurite length in P...
Elevated serum homocysteine (Hcys) is correlated with cardiovascular disease and with embryonic m... more Elevated serum homocysteine (Hcys) is correlated with cardiovascular disease and with embryonic malformations related to neural crest cells (NCCs). We predicted Hcys may alter the balance of actin networks, stress fibers and focal adhesions, altering migration. We cultured neural tube explants in control and Hcys-treated medium and visualized actin, α-actinin, vinculin, filamin, and LIM3 protein in NCCs migrating outward. In Hcys, phalloidin-stained actin in stress fibers was brighter, and vinculin was more abundant in focal adhesions and lamellipodia. α-actinin and LIM3 were also enhanced around nuclei and in focal adhesions, and α-actinin also in filopodia. Filamin was unchanged. Hcys caused more spreading and migration of NCCs, but not more cell-cell adhesions. The findings support our hypothesis that Hcys adjusts NCCs for greater adhesion and migration. Its effect on LIM3 suggests it may modulate signaling that adjusts the cytoskeleton for enhanced migration, leading to mistimed...
The macromolecules comprising the cytoskeleton and extracellular matrix of cells may be sensitive... more The macromolecules comprising the cytoskeleton and extracellular matrix of cells may be sensitive to gravitation. Since early development of organs depends on dynamic interactions across cell surfaces, altered gravity may disturb development. We investigated this possibility for heart development. Previous studies showed that the extracellular matrix glycoprotein fibronectin (Fn) is necessary for normal heart development. We cultured precardiac tissue explants in a high aspect ratio bioreactor vessel (HARV) to simulate microgravity. We observed tissue morphology, contraction, and Fn distribution by immunolocalization in HARV rotated and control (lxg) explants, cultured 18 hr. We also measured Fn amount by immunoassay. Explants in HARV were rotated at 6 rpm to achieve continuous freefall. Thirty-five of 37 control, but only 1 of 37 matched rotated explants exhibited contractions. Tissue architecture was identical. Immunolocalization of Fn showed remarkable differences which may be re...
Volume 11, Issue 1 and 2
All life on earth has developed and evolved in a unity gravity (1G) environment. Any deviation be... more All life on earth has developed and evolved in a unity gravity (1G) environment. Any deviation below or above 1G could affect animal development, a period when much change occurs and sensitivity is high. We imposed simulated hypergravity through centrifugation and analyzed the effects on the overall body length and cardiac growth of Xenopus laevis embryos. We predicted that increased contractile force would be required from the heart to adequately circulate blood, dispersing nutrients, and that this would inhibit organism growth and possibly induce a state of hypertrophy. Embryos reaching gastrulation stage were exposed to a 7G or 1G (control) field via centrifugation for 96 hours. We then recorded behavior, mortality and took body length measurements. We found no significant differences in behavior or mortality, however, body length was significantly reduced by an average of 6.8% in the 7G group. We then fixed, embedded, sectioned and stained embryos in order to investigate the dim...
Volume 12, Issue 2
Every living organism on earth has developed and evolved in unit gravity (1G) conditions. It is l... more Every living organism on earth has developed and evolved in unit gravity (1G) conditions. It is likely that any deviation from Earth’s standard gravity will influence development, particularly at early stages. Previous reports from this lab showed that total length is reduced and that ventricle size is increased during development at 7G. The objective of the present study was to investigate the effect of increasing levels of hypergravity on the development of the ventricular myocardial wall and the neuromuscular responsiveness of Xenopus laevis. At early gastrulation, embryos were placed in a centrifuge simulating 7G, 10G, 15G or 17G until they reached stage 45 (feeding tadpole stage, approximately 72 hours from initiation of gastrulation). Mortality was low and only the 17G exposure induced significant mortality. Immediately following centrifugation, the embryos were stimulated by touching with a probe to test neuromuscular responsiveness. With increasing G forces, responsiveness t...
Volume 7, Issue 2
Early amphibian development is sensitive to both reduced and elevated gravitational force. But la... more Early amphibian development is sensitive to both reduced and elevated gravitational force. But later, following gastrulation and neurulation, a critical population of cells must migrate from the dorsal neural tube outward to destinations throughout the body where they differentiate into a wide variety of critical tissues including head cartilage. These cells, the neural crest cells, respond to extracellular cues and signals that guide migration and differentiation in an intricate process that may also be sensitive to altered gravity. We examined the effects of hypergravity on the migration of neural crest cells to form head skeleton cartilage, and on body size in Xenopus embryos. To investigate this we centrifuged embryos at 7G or 10G, from yolk plug stage (gastrulation) through five days of development to stage 45 when feeding begins. A control group was placed on the centrifuge. After centrifugation, the embryos were fixed, cleared and stained with Alcian Blue to reveal cartilage....
Reproductive Toxicology, 1999
Journal of College Science Teaching, Jan 8, 2003
Cells Tissues Organs, 2016
Cellular and Molecular Biology of Mammary Cancer, 1987
The macromolecules comprising the cytoskeleton and extracellular matrix of cells may be sensitive... more The macromolecules comprising the cytoskeleton and extracellular matrix of cells may be sensitive to gravitation. Since early development of organs depends on dynamic interactions across cell surfaces, altered gravity may disturb development. We investigated this possibility for heart development. Previous studies showed that the extracellular matrix glycoprotein fibronectin (Fn) is necessary for normal heart development. We cultured precardiac tissue explants in a high aspect ratio bioreactor vessel (HARV) to simulate microgravity. We observed tissue morphology, contraction, and Fn distribution by immunolocalization in HARV rotated and control (lxg) explants, cultured 18 hr. We also measured Fn amount by immunoassay. Explants in HARV were rotated at 6 rpm to achieve continuous freefall. Thirty-five of 37 control, but only 1 of 37 matched rotated explants exhibited contractions. Tissue architecture was identical. Immunolocalization of Fn showed remarkable differences which may be re...
Typescript. Thesis (Ph. D.)--Kansas State University, 1982. Includes bibliographies. Microfilm.
Microscopy and Microanalysis, Aug 1, 1997
Formation of the chick heart is initiated when paired regions of the mesoderm migrate to a specif... more Formation of the chick heart is initiated when paired regions of the mesoderm migrate to a specific region in the primitive head. Certain cells eventually form a pair of endocardiac tubes that become the lining of the heart, while the remaining precardiac mesoderm ultimately differentiates into the myocardium. Fibronectin is suspected as a crucial component of the migratory process. Very few investigations have been conducted on the relationship between cell motility and microgravity.The primary objectives of this investigation were to determine the effect of altered gravity on the production and distribution of fibronectin, an extracellular matrix glycoprotein, during embryonic development of the chick heart, and to ascertain the extent to which these alterations affect myogenesis or morphogenesis. A microgravity bioreactor vessel, originally designed by NASA as a low-shear culture system, was employed to culture the cellular expiants in a simulated microgravity environment. Fertile, White-Leghorn chicken eggs were incubated at 38°C for 32 hours in a humidified egg incubator.
Annals of Behavioral Neuroscience, 2019
Background: Valproic acid (VPA) is an anti-convulsant drug used to treat seizures and a variety o... more Background: Valproic acid (VPA) is an anti-convulsant drug used to treat seizures and a variety of neural pathologies. Studies have shown that VPA exposure in rodent embryos leads to behavioral characteristics similar to those in humans with autism spectrum disorder (ASD). Utilizing this rodent model of ASD, research has led to a recognized mechanism of action of VPA involving brain overgrowth and hyperconnectivity, likely caused by epigenetic alteration of gene expression through inhibition of histone deacetylases.Objective: To gain further insight concerning this mechanism we modeled the development of neural connectivity at the cellular level.Method: We cultured dorsal root ganglia (DRGs) taken from eight-day old chick embryos in a range of VPA concentrations and investigated aspects of neuronal structure and behavior. DRGs were cultured 48 hours, fixed, and immunostained to reveal the locations of neural networks with synaptic vesicles.Results: We found a concentration-dependant...
Cadherin-11 (cad-11) is primarily a mesenchymal cadherin that appears in delaminating neural cres... more Cadherin-11 (cad-11) is primarily a mesenchymal cadherin that appears in delaminating neural crest cells. Its expression correlates with morphogenetic events and the pattern has been studied in mouse, rat and Xenopus embryos, but not during avian organogenesis. Our purpose was to investigate this pattern in the chick embryo during organogenesis using immunolocalization and in situ hybridization. Cad-11 was expressed in mesenchyme around the pharynx and aortic arches, eyes, auditory vesicles, lung buds, stomach, and nasal placodes. Neural expression included some cranial ganglia and also new neuroepithelium within the tail bud region undergoing secondary neurulation. We also found expression in epithelia of the developing circulatory and digestive organs. The limb buds, pineal rudiment and mesonephros were also positive. Cad-11 expression became more widespread with development. Our findings support the role of cad-11 as a mesenchymal cadherin, but provide evidence for a wider role t...
All life on earth has developed and evolved in a unity gravity (1G) environment. Any deviation be... more All life on earth has developed and evolved in a unity gravity (1G) environment. Any deviation below or above 1G could affect animal development, a period when much change occurs and sensitivity is high. We imposed simulated hypergravity through centrifugation and analyzed the effects on the overall body length and cardiac growth of Xenopus laevis embryos. We predicted that increased contractile force would be required from the heart to adequately circulate blood, dispersing nutrients, and that this would inhibit organism growth and possibly induce a state of hypertrophy. Embryos reaching gastrulation stage were exposed to a 7G or 1G (control) field via centrifugation for 96 hours. We then recorded behavior, mortality and took body length measurements. We found no significant differences in behavior or mortality, however, body length was significantly reduced by an average of 6.8% in the 7G group. We then fixed, embedded, sectioned and stained embryos in order to investigate the dim...
The vitamin folic acid (FA) is essential for DNA synthesis, repair and methylation, and for methi... more The vitamin folic acid (FA) is essential for DNA synthesis, repair and methylation, and for methionine synthesis. Although it is necessary for neural development, recent studies suggest a possible link between excess maternal supplemental FA intake and adverse interferences with single-carbon metabolism and neural development. Insufficient FA early in brain development can lead to failure of the neural tube closure, but the consequences of too much intake have not been fully investigated. Plasma FA concentrations can increase greatly with dietary supplementation. To model the development of neural connectivity, we cultured dorsal root ganglia (DRGs) taken from 8-day-old chick embryos in a range of pteroylmonoglutamate (PteGlu, synthetic supplemental FA) concentrations. DRGs were cultured for 36 h, fixed and immunostained to reveal the locations of neural networks with synaptic vesicles. We found a concentration-dependent relationship with significant reduction in neurite length in P...
Elevated serum homocysteine (Hcys) is correlated with cardiovascular disease and with embryonic m... more Elevated serum homocysteine (Hcys) is correlated with cardiovascular disease and with embryonic malformations related to neural crest cells (NCCs). We predicted Hcys may alter the balance of actin networks, stress fibers and focal adhesions, altering migration. We cultured neural tube explants in control and Hcys-treated medium and visualized actin, α-actinin, vinculin, filamin, and LIM3 protein in NCCs migrating outward. In Hcys, phalloidin-stained actin in stress fibers was brighter, and vinculin was more abundant in focal adhesions and lamellipodia. α-actinin and LIM3 were also enhanced around nuclei and in focal adhesions, and α-actinin also in filopodia. Filamin was unchanged. Hcys caused more spreading and migration of NCCs, but not more cell-cell adhesions. The findings support our hypothesis that Hcys adjusts NCCs for greater adhesion and migration. Its effect on LIM3 suggests it may modulate signaling that adjusts the cytoskeleton for enhanced migration, leading to mistimed...
The macromolecules comprising the cytoskeleton and extracellular matrix of cells may be sensitive... more The macromolecules comprising the cytoskeleton and extracellular matrix of cells may be sensitive to gravitation. Since early development of organs depends on dynamic interactions across cell surfaces, altered gravity may disturb development. We investigated this possibility for heart development. Previous studies showed that the extracellular matrix glycoprotein fibronectin (Fn) is necessary for normal heart development. We cultured precardiac tissue explants in a high aspect ratio bioreactor vessel (HARV) to simulate microgravity. We observed tissue morphology, contraction, and Fn distribution by immunolocalization in HARV rotated and control (lxg) explants, cultured 18 hr. We also measured Fn amount by immunoassay. Explants in HARV were rotated at 6 rpm to achieve continuous freefall. Thirty-five of 37 control, but only 1 of 37 matched rotated explants exhibited contractions. Tissue architecture was identical. Immunolocalization of Fn showed remarkable differences which may be re...
Volume 11, Issue 1 and 2
All life on earth has developed and evolved in a unity gravity (1G) environment. Any deviation be... more All life on earth has developed and evolved in a unity gravity (1G) environment. Any deviation below or above 1G could affect animal development, a period when much change occurs and sensitivity is high. We imposed simulated hypergravity through centrifugation and analyzed the effects on the overall body length and cardiac growth of Xenopus laevis embryos. We predicted that increased contractile force would be required from the heart to adequately circulate blood, dispersing nutrients, and that this would inhibit organism growth and possibly induce a state of hypertrophy. Embryos reaching gastrulation stage were exposed to a 7G or 1G (control) field via centrifugation for 96 hours. We then recorded behavior, mortality and took body length measurements. We found no significant differences in behavior or mortality, however, body length was significantly reduced by an average of 6.8% in the 7G group. We then fixed, embedded, sectioned and stained embryos in order to investigate the dim...
Volume 12, Issue 2
Every living organism on earth has developed and evolved in unit gravity (1G) conditions. It is l... more Every living organism on earth has developed and evolved in unit gravity (1G) conditions. It is likely that any deviation from Earth’s standard gravity will influence development, particularly at early stages. Previous reports from this lab showed that total length is reduced and that ventricle size is increased during development at 7G. The objective of the present study was to investigate the effect of increasing levels of hypergravity on the development of the ventricular myocardial wall and the neuromuscular responsiveness of Xenopus laevis. At early gastrulation, embryos were placed in a centrifuge simulating 7G, 10G, 15G or 17G until they reached stage 45 (feeding tadpole stage, approximately 72 hours from initiation of gastrulation). Mortality was low and only the 17G exposure induced significant mortality. Immediately following centrifugation, the embryos were stimulated by touching with a probe to test neuromuscular responsiveness. With increasing G forces, responsiveness t...
Volume 7, Issue 2
Early amphibian development is sensitive to both reduced and elevated gravitational force. But la... more Early amphibian development is sensitive to both reduced and elevated gravitational force. But later, following gastrulation and neurulation, a critical population of cells must migrate from the dorsal neural tube outward to destinations throughout the body where they differentiate into a wide variety of critical tissues including head cartilage. These cells, the neural crest cells, respond to extracellular cues and signals that guide migration and differentiation in an intricate process that may also be sensitive to altered gravity. We examined the effects of hypergravity on the migration of neural crest cells to form head skeleton cartilage, and on body size in Xenopus embryos. To investigate this we centrifuged embryos at 7G or 10G, from yolk plug stage (gastrulation) through five days of development to stage 45 when feeding begins. A control group was placed on the centrifuge. After centrifugation, the embryos were fixed, cleared and stained with Alcian Blue to reveal cartilage....
Reproductive Toxicology, 1999
Journal of College Science Teaching, Jan 8, 2003
Cells Tissues Organs, 2016
Cellular and Molecular Biology of Mammary Cancer, 1987
The macromolecules comprising the cytoskeleton and extracellular matrix of cells may be sensitive... more The macromolecules comprising the cytoskeleton and extracellular matrix of cells may be sensitive to gravitation. Since early development of organs depends on dynamic interactions across cell surfaces, altered gravity may disturb development. We investigated this possibility for heart development. Previous studies showed that the extracellular matrix glycoprotein fibronectin (Fn) is necessary for normal heart development. We cultured precardiac tissue explants in a high aspect ratio bioreactor vessel (HARV) to simulate microgravity. We observed tissue morphology, contraction, and Fn distribution by immunolocalization in HARV rotated and control (lxg) explants, cultured 18 hr. We also measured Fn amount by immunoassay. Explants in HARV were rotated at 6 rpm to achieve continuous freefall. Thirty-five of 37 control, but only 1 of 37 matched rotated explants exhibited contractions. Tissue architecture was identical. Immunolocalization of Fn showed remarkable differences which may be re...
Typescript. Thesis (Ph. D.)--Kansas State University, 1982. Includes bibliographies. Microfilm.