Beate Brand-Saberi - Academia.edu (original) (raw)

Papers by Beate Brand-Saberi

Research paper thumbnail of Vertebrate myogenesis : stem cells and precursors

Springer eBooks, 2015

Recruitment of skeletal muscle progenitors to secondary sites: A role for CXCR4/SDF-1 signaling i... more Recruitment of skeletal muscle progenitors to secondary sites: A role for CXCR4/SDF-1 signaling in skeletal muscle development.- Hypaxial muscle - controversial classification and controversial data? Skeletal Myogenesis in the Zebrafish and its Implications for Muscle Disease Modeling.- Mechanisms of Myogenic Specification and Patterning.- The avian embryo as a model system for skeletal myogenesis.- Head Muscle Development.- The lateral plate mesoderm - a novel source of skeletal muscle.- Regulation of skeletal muscle development and disease by microRNAs.- Adult skeletal muscle stem cells.- Dormancy and quiescence of skeletal muscle stem cells.

Research paper thumbnail of Cell survival controlled by lens‐derived Sema3A–Nrp1 is vital on caffeine‐suppressed corneal innervation during chick organogenesis

Journal of Cellular Physiology, Oct 26, 2018

In this study, we investigated the effect of caffeine overexposure on corneal innervation in the ... more In this study, we investigated the effect of caffeine overexposure on corneal innervation in the early chicken embryo. Caffeine administration restricted corneal innervation by affecting trigeminal nerve development. Immunohistochemistry for phospho-Histone3 (pHIS3) and C-caspase3 revealed that cell survival was repressed by caffeine administration. Whole-mount in situ hybridization against semaphorin 3A (Sema3A) and neuropilin-1 (Nrp1) showed that both caffeine and 2,2′-azobis(2-methylpropionamidine) dihydrochloride (AAPH, a free radical generator) administration upregulates the expression of both Sema3A and Nrp1. Next, we demonstrated that lens ablation in the developing chicken embryos significantly affected NF-labeled periocular nerve fascicles and innervation to the central eye region. Subsequently, we used a neuroblastoma cell line to investigate in vitro whether or not Sema3A-Nrp1 signaling exerts a key role on the caffeine-suppressed neuron survival. Knocking-down Sema3A through transfection with Sema3A-siRNA dramatically decreased the responsiveness of cells to caffeine administration, as well as cell apoptosis. We suggest that Sema3A-Nrp1 signaling regulates Trp53 and Cdkn1a through Slit2-Robo1 and Ephb2. Taken together, we speculate here that caffeineenhanced reactive oxygen species upregulates Sema3A-Nrp1 expression in the lens and periocular tissues, resulting in corneal cell apoptosis, accompanied by its chemorepellent role on the invasion of the developing cornea by trigeminal sensory fibers.

Research paper thumbnail of Inhibition of myogenic cell migration by the application of antibodies raised against limb bud mesenchyme

Research paper thumbnail of Observations Concerning the Control of Directed Myogenic Cell Migration

Springer eBooks, 1991

Between the third and fifth day of development, the limb buds of avian embryos are invaded by a c... more Between the third and fifth day of development, the limb buds of avian embryos are invaded by a cell population originating from the ventrolateral edges of the adjacent dermomyotomes at wing and leg level (Christ et al. 1974, 1977, 1983; Chevallier et al. 1976; Jacob et al. 1978, 1979). These cells are known to be the precursor cells of the skeletal limb muscles. Due to their site of origin near the embryonic body axis and their destination in the limbs, the myogenic cells initially have to migrate from a medial to a more lateral position across the space between the somites and the somatopleural mesenchyme. Once they have reached the limb anlagen, the myogenic cells migrate towards the tips of the outgrowing buds (Wachtler et al. 1981, 1982; Brand et al. 1985).

Research paper thumbnail of Decreased sympathetic cardiovascular influences and hormone‐physiological changes in response to Covid‐19‐related adaptations under different learning environments

Anatomical Sciences Education, Aug 1, 2022

Research paper thumbnail of Changes of cytokeratin expression in the epidermis with chronic venous insufficiency

PubMed, May 1, 1997

Background: A specific, individual pattern of cytokeratins (Cks) is expressed by each epithelial ... more Background: A specific, individual pattern of cytokeratins (Cks) is expressed by each epithelial cells as part of the cytoskeleton. Cks are established as markers of epidermal differentiation. Basal cells are characterized by CK5 and 14 expression, whereas CK 1, 10 and 11 are typical for the suprabasal compartment of normal epidermis. Here, we investigated changes of Pan-CK, CK 10, and CK 14 expression in the epidermis in various stages of chronic venous insufficiency (CVI). Patients and methods: In punch biopsies of 24 patients with chronic venous insufficiency and of 6 volunteers with normal skin Cks were detected by indirect immunofluorescence using monoclonal antibodies against CK 10, CK 14 and Pan-CK. Results: CK 10 and Pan-CK staining intensity increased with the severity of CVI changes. Suprabasal cells showed an upregulation of CK 10 and Pan-CK expression first in venous eczema. CK 14 expression is under normal condition confined to the basal cell layer of the epidermis. However in venous eczema and lipodermatosclerosis, CK 14 is detected in the suprabasal epidermal compartment. Conclusions: It is therefore concluded that altered differentiation and stratification mechanisms occur in keratinocytes in the epidermis with CVI first detectable in the stage of venous eczema. These changes are accompanied by a characteristic CK expression pattern.

Research paper thumbnail of CNTF and Nrf2 Are Coordinately Involved in Regulating Self-Renewal and Differentiation of Neural Stem Cell during Embryonic Development

iScience, Sep 1, 2019

There is high risk of fetal neurodevelopmental defects in pregestational diabetes mellitus (PGDM)... more There is high risk of fetal neurodevelopmental defects in pregestational diabetes mellitus (PGDM). However, the effective mechanism of hyperglycemia-induced neurodevelopmental negative effects, including neural stem cell self-renewal and differentiation, still remains obscure. Neuropoietic cytokines have been shown to play a vital part during nervous system development and in the coordination of neurons and gliocytes. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) dysfunction might be related to a reduction of self-protective response in brain malformation induced by hyperglycemia. We therefore evaluated the role of Nrf2 and neuropoietic cytokines in fetal neurodevelopmental defects induced by PGDM and determined the mechanisms involved. Our data reveal that PGDM dramatically impairs the developmental switch of neural stem cells from neurogenesis to gliogenesis, principally under the cooperative mediation of neuropoietic cytokine CNTF and Nrf2 antioxidative signaling. This indicates that CNTF and Nrf2 could be potentially used in the prevention or therapy of neurodevelopmental defects of PGDM offspring.

Research paper thumbnail of Development of the embryonic vascular system

PubMed, 1995

In this article, we survey the mechanisms involved in early embryonic angiogenesis. The first emb... more In this article, we survey the mechanisms involved in early embryonic angiogenesis. The first embryonic blood vessels are formed exclusively by endothelial cells. Therefore, the emergence and behavior of this cell type is the center of this article. We discuss both intra- and extraembryonic angiogenesis and the various modes of capillary formation. The high plasticity and migratory potential of endothelial cells and their precursors, the angioblists, are outlined. The promoting and inhibiting influences of the extracellular matrix on the behavior of angioblasts are a matter of concern, as is also the question of embryonic angiogenic factors. Cell-cell interactions that may lead to organ-specific differentiation of endothelial cells are mainly discussed in the context of blood-brain barrier formation and development of fenestrated capillaries. The last section deals with the development of the vascular wall.

Research paper thumbnail of Zinc oxide nanoparticles exposure-induced oxidative stress restricts cranial neural crest development during chicken embryogenesis

Ecotoxicology and Environmental Safety, May 1, 2020

Research paper thumbnail of The formation of somite compartments in the avian embryo

PubMed, Feb 1, 1996

The somites develop from the unsegmented paraxial mesoderm that flanks the neural tube. They form... more The somites develop from the unsegmented paraxial mesoderm that flanks the neural tube. They form in an intrinsic process which lays down the primary segmental pattern of the vertebrate body. We review the processes of somitogenesis and somite differentiation as well as the mechanisms involved in these developmental events. Long before overt differentiation occurs, different compartments of the still epithelial somites give rise to special cell lines and to particular derivatives. By means of isotypic grafting between quail and chick embryos, it is possible to follow the fate of groups of somitic cells. In this way, the development of the myotome and the back dermis from the dorsomedial quadrant and of the hypaxial body wall and limb musculature from the dorsolateral quadrant was established. The two ventral quadrants and the somitocoele give rise to the chondrogenic/fibroblastic lineage of the sclerotome and form the vertebral column. Somite compartments can first be visualized by the expression pattern of Pax genes. Pax-3 is expressed in the dorsal part of the epithelial somite, while the ventral two thirds express Pax-1, a marker of sclerotome development. Pax-3 expression is retained also in the premitotic myogenic cells that migrate into the limb buds. In differentiating myoblasts, Pax-3 expression is turned down and taken over by the activation of MDF's. This initial event in myogenesis occurs in the absence of local signals, whereas the expression of Pax-1 in the sclerotome can be shown to be induced by signals from the notochord and floor-plate of the neural tube. Epaxial myotome differentiation is supported by the neural tube, after the neural tube has received patterning signals from the notochord. The hypaxial musculature and limb musculature differentiate independently of the axial structures. The myogenic cells migrating within the limb buds respond to signals of the lateral plate mesoderm which guide their distalward migration and pattern the muscle.

Research paper thumbnail of Expression of thymosin beta4 during chick development

Anatomy and Embryology, Apr 1, 2004

We cloned the chick homologue of Homo sapiens thymosin beta4, encoding a G-actin sequestering fac... more We cloned the chick homologue of Homo sapiens thymosin beta4, encoding a G-actin sequestering factor which plays an important role in angiogenesis, cell motility and tumorigenesis. The thymosin beta4 gene is highly conserved between chick and human. Its expression was analyzed during different stages of development. At early stages thymosin beta4 is expressed in the mesoderm and endoderm and in Hensen's node. Later, thymosin beta4 transcripts are found in the head mesenchyme, somites, dorsal root ganglia, neural tube, brain, blood vessels and feather buds. The pattern of thymosin beta4 expression in blood vessels indicates a function mainly in development of the blood circulatory system which closely parallels findings in vitro. The observed expression pattern shows a high similarity to expression data published for mice, mainly in the heart and in the nervous system. Important new aspects are the early onset of expression, the expression in the mesoderm preceding heart formation and the involvement in feather development.

Research paper thumbnail of Kinetics and differentiation of somite cells forming the vertebral column: studies on human and chick embryos

Anatomy and Embryology, Dec 1, 1994

We have studied the kinetics of somite cells with an antibody against proliferating cell nuclear ... more We have studied the kinetics of somite cells with an antibody against proliferating cell nuclear antigen (PCNA/cyclin) in human and chick embryos, and with the BrdU anti-BrdU method in chick embryos, to investigate whether the metameric pattern of the developing vertebral column can be explained by different proliferation rates. Furthermore we applied antibodies against differentiation markers of chondrogenic and myogenic cells of the somites in order to study the correlation between proliferation and differentiation. There are no principal differences in the proliferation pattern of the vertebral column between human and chick embryos. In all stages examined, the cell density is higher in the caudal sclerotome halves than in the cranial halves. Laterally, the caudal sclerotome halves, which give rise to the neural arches, are characterized by a higher proliferative activity than the cranial halves. Although there is a high variability, the labelling indices show significant differences between the two halves with both proliferation markers. With the onset of chondrogenic differentiation, only the perichondrial cells retain a high proliferation rate. During fetal development, the neural arches and their processes grow appositionally. Even at the earliest stages, there is practically no immunostaining for PCNA or BrdU in the desmin-positive myotome cells of human and chick embryos. Axially, a higher proliferation rate is found in the condensed mesenchyme of the anlagen of the intervertebral discs than in the anlagen of the vertebral bodies. During fetal development, cells at the borders between vertebral bodies and intervertebral discs proliferate, indicating appositional growth.(ABSTRACT TRUNCATED AT 250 WORDS)

Research paper thumbnail of Hyaluronic acid influences the migration of myoblasts within the avian embryonic wing bud

American Journal of Anatomy, Dec 1, 1991

Myoblasts migrate in a proximodistal direction within the avian embryonic wing bud during normal ... more Myoblasts migrate in a proximodistal direction within the avian embryonic wing bud during normal limb development. Since the presence and distribution of hyaluronic acid within the wing bud coincide with the time and with the direction of the migration of myoblasts, we microinjected hyaluronic acid into chicken wing buds that had received grafts containing quail myoblasts. It was found that injected hyaluronic acid has a strong positive effect on the migration of myoblasts: it causes a migration of myoblasts in donor-host combinations in which this is normally not the case, and it can cause migration in a proximal direction, a phenomenon not observed during normal development. From this it may be concluded that hyaluronic acid can influence myoblast migration in vivo. A similar effect could be observed after the microinjection of dextran sulfate, a synthetic compound having similar physicochemical properties. Hyaluronic acid, therefore, may play an important role in the control of the migration of myogenic cells in vivo by its physicochemical properties.

Research paper thumbnail of Limb muscle development

PubMed, 2002

Skeletal muscle precursors for the limbs originate from the epithelial layer of the somites, the ... more Skeletal muscle precursors for the limbs originate from the epithelial layer of the somites, the dermomyotomes. We summarize the steps of limb muscle development from the specification of precursor cells in the dermomyotome, the directed migration of these cells to and within the limb buds to muscle growth and differentiation. All steps are controlled by local signaling between embryonic structures. In dermomyotome development, signals from the neural tube, the ectoderm and the intermediate and lateral mesoderm result in a medio-lateral patterning. Only the lateral portions of the dermomyotomes give rise to muscle precursor cells destined to enter the limb buds. As a prerequisite for migration, precursor cells have to de-epithelialize as a result of interactions between SF/HGF and its receptor c-met. Precursor cells adopt a mesenchymal morphology without losing their myogenic specification. This is achieved by the expression of the transcription factors Pax3, Pax7 and myf5. During migration, premature differentiation has to be kept at bay to enable motility and proliferation. After having reached their target sites, the dorsal and ventral myogenic zones, myogenesis is initiated by the activation of the muscle determination factors MyoD, myogenin and MRF4. Finally, we briefly summarize the process of muscle hypertrophy and regeneration during which aspects of developmental processes are reinitiated.

Research paper thumbnail of Function of Somite and Somitocoele Cells in the Formation of the Vertebral Motion Segment in Avian Embryos

Cells Tissues Organs, 1996

We have studied the distribution of thoracic somite and somitocoele-derived cells using homotopic... more We have studied the distribution of thoracic somite and somitocoele-derived cells using homotopical grafting between quail and chicken embryos and rein-cubation periods of 2-6 days. Serial sections were evaluated with antibodies against quail cells, quail hemangiopoietic cells and desmin. With the exception of neural crest cells in the cranial sclerotome half, all cells of the operated segment are quail cells derived from a single somite. These cells differentiate into sclerotome, myotome and the anlage of the dermis of the back. After longer re-incubation periods, the somite-derived quail cells form the neighboring halves of 2 adjacent vertebral bodies and the intervening (disc-homologous) tissue. Resegmentation is furthermore visible in the lamina and the spinous process. Somite cells also form the articular and transverse processes, and the intertransverse muscle including its insertion to the next cranial transverse process. One thoracic somite forms the proximal part of 1 rib. In more distal parts, 1 somite forms the cranial half of 1 rib and the caudal half of the next cranial rib, and the intercostal muscle and part of the connective tissue. Somite-derived quail cells are found in muscle that bridges over 2 segments cranial and caudal from the operated segment. The craniocaudal distribution of endothelial cells is approximately the same. Somitocoele cells that are located centrally in the epithelial somite express the sclerotome-markers Pax-1 and Pax-9. After 2-3 days of reincubation, grafted thoracic somitocoele cells are found mainly in the cranial part of the caudal sclerotome half. They form an area representing the anlagen of the intervertebral disc and the rib. After longer reincubation periods, the grafted quail somitocoele cells form the intervertebral disc-homologous tissue and the proximal part of the rib. In more distal parts of the rib they are located in the cranial half of 1 rib and the caudal half of the next cranial rib. The somitocoele cells also form the surface of the intervertebral joint, and give rise to a small number of endothelial cells that are found up to 1 segment cranial and caudal to the operation site. Our studies show that resegmentation is found in most parts of the vertebra and in the distal ribs. One somite forms the origin and insertion of the segmental muscle. Therefore, the somite can be regarded as the ancestor of the vertebral motion segment. Somitocoele cells are located centrally both in the epithelial somite and in the vertebral motion segment.

Research paper thumbnail of 1 Evolution and Development of Distinct Cell Lineages Derived from Somites

Current Topics in Developmental Biology, 1999

... There is no sharp boundary between the 36 Beate Brand-Saberi and Bodo Christ Figure 37 Whole ... more ... There is no sharp boundary between the 36 Beate Brand-Saberi and Bodo Christ Figure 37 Whole mount in situ hybridization of a 2-day chick embryo for VEGFR !I (Quek I ) (magnification: X50). ... Christ, B., Jacob, M., and Jacob, HJ (1983). On the origin and development of ...

Research paper thumbnail of Sclerotomal origin of the ribs

Research paper thumbnail of Regulation ofparaxisExpression and Somite Formation by Ectoderm- and Neural Tube-Derived Signals

Developmental Biology, May 1, 1997

During vertebrate embryogenesis, the paraxial mesoderm becomes segmented into somites, which form... more During vertebrate embryogenesis, the paraxial mesoderm becomes segmented into somites, which form as paired epithelial spheres with a periodicity that reflects the segmental organization of the embryo. As a somite matures, the ventral region gives rise to a mesenchymal cell population, the sclerotome, that forms the axial skeleton. The dorsal region of the somite remains epithelial and is called dermomyotome. The dermomyotome gives rise to the trunk and limb muscle and to the dermis of the back. Epaxial and hypaxial muscle precursors can be attributed to distinct somitic compartments which are laid down prior to overt somite differentiation. Inductive signals from the neural tube, notochord, and overlying ectoderm have been shown to be required for patterning of the somites into these different compartments. Paraxis is a basic helixloop-helix transcription factor expressed in the unsegmented paraxial mesoderm and throughout epithelial somites before becoming restricted to epithelial cells of the dermomyotome. To determine whether paraxis might be a target for inductive signals that influence somite patterning, we examined the influence of axial structures and surface ectoderm on paraxis expression by performing microsurgical operations on chick embryos. These studies revealed two distinct phases of paraxis expression, an early phase in the paraxial mesoderm that is dependent on signals from the ectoderm and independent of the neural tube, and a later phase that is supported by redundant signals from the ectoderm and neural tube. Under experimental conditions in which paraxis failed to be expressed, cells from the paraxial mesoderm failed to epithelialize and somites were not formed. We also performed an RT-PCR analysis of combined tissue explants in vitro and confirmed that surface ectoderm is sufficient to induce paraxis expression in segmental plate mesoderm. These results demonstrate that somite formation requires signals from adjacent cell types and that the paraxis gene is a target for the signal transduction pathways that regulate somitogenesis. ᭧ 1997 Academic Press Sequence data from this article have been deposited with the EMBL/GenBank Data Libraries under Accession No. U76665.

Research paper thumbnail of Kapitel 4: Kopf und Hals

Research paper thumbnail of Kapitel 10: Sinnesorgane: Auge und Ohr

Research paper thumbnail of Vertebrate myogenesis : stem cells and precursors

Springer eBooks, 2015

Recruitment of skeletal muscle progenitors to secondary sites: A role for CXCR4/SDF-1 signaling i... more Recruitment of skeletal muscle progenitors to secondary sites: A role for CXCR4/SDF-1 signaling in skeletal muscle development.- Hypaxial muscle - controversial classification and controversial data? Skeletal Myogenesis in the Zebrafish and its Implications for Muscle Disease Modeling.- Mechanisms of Myogenic Specification and Patterning.- The avian embryo as a model system for skeletal myogenesis.- Head Muscle Development.- The lateral plate mesoderm - a novel source of skeletal muscle.- Regulation of skeletal muscle development and disease by microRNAs.- Adult skeletal muscle stem cells.- Dormancy and quiescence of skeletal muscle stem cells.

Research paper thumbnail of Cell survival controlled by lens‐derived Sema3A–Nrp1 is vital on caffeine‐suppressed corneal innervation during chick organogenesis

Journal of Cellular Physiology, Oct 26, 2018

In this study, we investigated the effect of caffeine overexposure on corneal innervation in the ... more In this study, we investigated the effect of caffeine overexposure on corneal innervation in the early chicken embryo. Caffeine administration restricted corneal innervation by affecting trigeminal nerve development. Immunohistochemistry for phospho-Histone3 (pHIS3) and C-caspase3 revealed that cell survival was repressed by caffeine administration. Whole-mount in situ hybridization against semaphorin 3A (Sema3A) and neuropilin-1 (Nrp1) showed that both caffeine and 2,2′-azobis(2-methylpropionamidine) dihydrochloride (AAPH, a free radical generator) administration upregulates the expression of both Sema3A and Nrp1. Next, we demonstrated that lens ablation in the developing chicken embryos significantly affected NF-labeled periocular nerve fascicles and innervation to the central eye region. Subsequently, we used a neuroblastoma cell line to investigate in vitro whether or not Sema3A-Nrp1 signaling exerts a key role on the caffeine-suppressed neuron survival. Knocking-down Sema3A through transfection with Sema3A-siRNA dramatically decreased the responsiveness of cells to caffeine administration, as well as cell apoptosis. We suggest that Sema3A-Nrp1 signaling regulates Trp53 and Cdkn1a through Slit2-Robo1 and Ephb2. Taken together, we speculate here that caffeineenhanced reactive oxygen species upregulates Sema3A-Nrp1 expression in the lens and periocular tissues, resulting in corneal cell apoptosis, accompanied by its chemorepellent role on the invasion of the developing cornea by trigeminal sensory fibers.

Research paper thumbnail of Inhibition of myogenic cell migration by the application of antibodies raised against limb bud mesenchyme

Research paper thumbnail of Observations Concerning the Control of Directed Myogenic Cell Migration

Springer eBooks, 1991

Between the third and fifth day of development, the limb buds of avian embryos are invaded by a c... more Between the third and fifth day of development, the limb buds of avian embryos are invaded by a cell population originating from the ventrolateral edges of the adjacent dermomyotomes at wing and leg level (Christ et al. 1974, 1977, 1983; Chevallier et al. 1976; Jacob et al. 1978, 1979). These cells are known to be the precursor cells of the skeletal limb muscles. Due to their site of origin near the embryonic body axis and their destination in the limbs, the myogenic cells initially have to migrate from a medial to a more lateral position across the space between the somites and the somatopleural mesenchyme. Once they have reached the limb anlagen, the myogenic cells migrate towards the tips of the outgrowing buds (Wachtler et al. 1981, 1982; Brand et al. 1985).

Research paper thumbnail of Decreased sympathetic cardiovascular influences and hormone‐physiological changes in response to Covid‐19‐related adaptations under different learning environments

Anatomical Sciences Education, Aug 1, 2022

Research paper thumbnail of Changes of cytokeratin expression in the epidermis with chronic venous insufficiency

PubMed, May 1, 1997

Background: A specific, individual pattern of cytokeratins (Cks) is expressed by each epithelial ... more Background: A specific, individual pattern of cytokeratins (Cks) is expressed by each epithelial cells as part of the cytoskeleton. Cks are established as markers of epidermal differentiation. Basal cells are characterized by CK5 and 14 expression, whereas CK 1, 10 and 11 are typical for the suprabasal compartment of normal epidermis. Here, we investigated changes of Pan-CK, CK 10, and CK 14 expression in the epidermis in various stages of chronic venous insufficiency (CVI). Patients and methods: In punch biopsies of 24 patients with chronic venous insufficiency and of 6 volunteers with normal skin Cks were detected by indirect immunofluorescence using monoclonal antibodies against CK 10, CK 14 and Pan-CK. Results: CK 10 and Pan-CK staining intensity increased with the severity of CVI changes. Suprabasal cells showed an upregulation of CK 10 and Pan-CK expression first in venous eczema. CK 14 expression is under normal condition confined to the basal cell layer of the epidermis. However in venous eczema and lipodermatosclerosis, CK 14 is detected in the suprabasal epidermal compartment. Conclusions: It is therefore concluded that altered differentiation and stratification mechanisms occur in keratinocytes in the epidermis with CVI first detectable in the stage of venous eczema. These changes are accompanied by a characteristic CK expression pattern.

Research paper thumbnail of CNTF and Nrf2 Are Coordinately Involved in Regulating Self-Renewal and Differentiation of Neural Stem Cell during Embryonic Development

iScience, Sep 1, 2019

There is high risk of fetal neurodevelopmental defects in pregestational diabetes mellitus (PGDM)... more There is high risk of fetal neurodevelopmental defects in pregestational diabetes mellitus (PGDM). However, the effective mechanism of hyperglycemia-induced neurodevelopmental negative effects, including neural stem cell self-renewal and differentiation, still remains obscure. Neuropoietic cytokines have been shown to play a vital part during nervous system development and in the coordination of neurons and gliocytes. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) dysfunction might be related to a reduction of self-protective response in brain malformation induced by hyperglycemia. We therefore evaluated the role of Nrf2 and neuropoietic cytokines in fetal neurodevelopmental defects induced by PGDM and determined the mechanisms involved. Our data reveal that PGDM dramatically impairs the developmental switch of neural stem cells from neurogenesis to gliogenesis, principally under the cooperative mediation of neuropoietic cytokine CNTF and Nrf2 antioxidative signaling. This indicates that CNTF and Nrf2 could be potentially used in the prevention or therapy of neurodevelopmental defects of PGDM offspring.

Research paper thumbnail of Development of the embryonic vascular system

PubMed, 1995

In this article, we survey the mechanisms involved in early embryonic angiogenesis. The first emb... more In this article, we survey the mechanisms involved in early embryonic angiogenesis. The first embryonic blood vessels are formed exclusively by endothelial cells. Therefore, the emergence and behavior of this cell type is the center of this article. We discuss both intra- and extraembryonic angiogenesis and the various modes of capillary formation. The high plasticity and migratory potential of endothelial cells and their precursors, the angioblists, are outlined. The promoting and inhibiting influences of the extracellular matrix on the behavior of angioblasts are a matter of concern, as is also the question of embryonic angiogenic factors. Cell-cell interactions that may lead to organ-specific differentiation of endothelial cells are mainly discussed in the context of blood-brain barrier formation and development of fenestrated capillaries. The last section deals with the development of the vascular wall.

Research paper thumbnail of Zinc oxide nanoparticles exposure-induced oxidative stress restricts cranial neural crest development during chicken embryogenesis

Ecotoxicology and Environmental Safety, May 1, 2020

Research paper thumbnail of The formation of somite compartments in the avian embryo

PubMed, Feb 1, 1996

The somites develop from the unsegmented paraxial mesoderm that flanks the neural tube. They form... more The somites develop from the unsegmented paraxial mesoderm that flanks the neural tube. They form in an intrinsic process which lays down the primary segmental pattern of the vertebrate body. We review the processes of somitogenesis and somite differentiation as well as the mechanisms involved in these developmental events. Long before overt differentiation occurs, different compartments of the still epithelial somites give rise to special cell lines and to particular derivatives. By means of isotypic grafting between quail and chick embryos, it is possible to follow the fate of groups of somitic cells. In this way, the development of the myotome and the back dermis from the dorsomedial quadrant and of the hypaxial body wall and limb musculature from the dorsolateral quadrant was established. The two ventral quadrants and the somitocoele give rise to the chondrogenic/fibroblastic lineage of the sclerotome and form the vertebral column. Somite compartments can first be visualized by the expression pattern of Pax genes. Pax-3 is expressed in the dorsal part of the epithelial somite, while the ventral two thirds express Pax-1, a marker of sclerotome development. Pax-3 expression is retained also in the premitotic myogenic cells that migrate into the limb buds. In differentiating myoblasts, Pax-3 expression is turned down and taken over by the activation of MDF's. This initial event in myogenesis occurs in the absence of local signals, whereas the expression of Pax-1 in the sclerotome can be shown to be induced by signals from the notochord and floor-plate of the neural tube. Epaxial myotome differentiation is supported by the neural tube, after the neural tube has received patterning signals from the notochord. The hypaxial musculature and limb musculature differentiate independently of the axial structures. The myogenic cells migrating within the limb buds respond to signals of the lateral plate mesoderm which guide their distalward migration and pattern the muscle.

Research paper thumbnail of Expression of thymosin beta4 during chick development

Anatomy and Embryology, Apr 1, 2004

We cloned the chick homologue of Homo sapiens thymosin beta4, encoding a G-actin sequestering fac... more We cloned the chick homologue of Homo sapiens thymosin beta4, encoding a G-actin sequestering factor which plays an important role in angiogenesis, cell motility and tumorigenesis. The thymosin beta4 gene is highly conserved between chick and human. Its expression was analyzed during different stages of development. At early stages thymosin beta4 is expressed in the mesoderm and endoderm and in Hensen's node. Later, thymosin beta4 transcripts are found in the head mesenchyme, somites, dorsal root ganglia, neural tube, brain, blood vessels and feather buds. The pattern of thymosin beta4 expression in blood vessels indicates a function mainly in development of the blood circulatory system which closely parallels findings in vitro. The observed expression pattern shows a high similarity to expression data published for mice, mainly in the heart and in the nervous system. Important new aspects are the early onset of expression, the expression in the mesoderm preceding heart formation and the involvement in feather development.

Research paper thumbnail of Kinetics and differentiation of somite cells forming the vertebral column: studies on human and chick embryos

Anatomy and Embryology, Dec 1, 1994

We have studied the kinetics of somite cells with an antibody against proliferating cell nuclear ... more We have studied the kinetics of somite cells with an antibody against proliferating cell nuclear antigen (PCNA/cyclin) in human and chick embryos, and with the BrdU anti-BrdU method in chick embryos, to investigate whether the metameric pattern of the developing vertebral column can be explained by different proliferation rates. Furthermore we applied antibodies against differentiation markers of chondrogenic and myogenic cells of the somites in order to study the correlation between proliferation and differentiation. There are no principal differences in the proliferation pattern of the vertebral column between human and chick embryos. In all stages examined, the cell density is higher in the caudal sclerotome halves than in the cranial halves. Laterally, the caudal sclerotome halves, which give rise to the neural arches, are characterized by a higher proliferative activity than the cranial halves. Although there is a high variability, the labelling indices show significant differences between the two halves with both proliferation markers. With the onset of chondrogenic differentiation, only the perichondrial cells retain a high proliferation rate. During fetal development, the neural arches and their processes grow appositionally. Even at the earliest stages, there is practically no immunostaining for PCNA or BrdU in the desmin-positive myotome cells of human and chick embryos. Axially, a higher proliferation rate is found in the condensed mesenchyme of the anlagen of the intervertebral discs than in the anlagen of the vertebral bodies. During fetal development, cells at the borders between vertebral bodies and intervertebral discs proliferate, indicating appositional growth.(ABSTRACT TRUNCATED AT 250 WORDS)

Research paper thumbnail of Hyaluronic acid influences the migration of myoblasts within the avian embryonic wing bud

American Journal of Anatomy, Dec 1, 1991

Myoblasts migrate in a proximodistal direction within the avian embryonic wing bud during normal ... more Myoblasts migrate in a proximodistal direction within the avian embryonic wing bud during normal limb development. Since the presence and distribution of hyaluronic acid within the wing bud coincide with the time and with the direction of the migration of myoblasts, we microinjected hyaluronic acid into chicken wing buds that had received grafts containing quail myoblasts. It was found that injected hyaluronic acid has a strong positive effect on the migration of myoblasts: it causes a migration of myoblasts in donor-host combinations in which this is normally not the case, and it can cause migration in a proximal direction, a phenomenon not observed during normal development. From this it may be concluded that hyaluronic acid can influence myoblast migration in vivo. A similar effect could be observed after the microinjection of dextran sulfate, a synthetic compound having similar physicochemical properties. Hyaluronic acid, therefore, may play an important role in the control of the migration of myogenic cells in vivo by its physicochemical properties.

Research paper thumbnail of Limb muscle development

PubMed, 2002

Skeletal muscle precursors for the limbs originate from the epithelial layer of the somites, the ... more Skeletal muscle precursors for the limbs originate from the epithelial layer of the somites, the dermomyotomes. We summarize the steps of limb muscle development from the specification of precursor cells in the dermomyotome, the directed migration of these cells to and within the limb buds to muscle growth and differentiation. All steps are controlled by local signaling between embryonic structures. In dermomyotome development, signals from the neural tube, the ectoderm and the intermediate and lateral mesoderm result in a medio-lateral patterning. Only the lateral portions of the dermomyotomes give rise to muscle precursor cells destined to enter the limb buds. As a prerequisite for migration, precursor cells have to de-epithelialize as a result of interactions between SF/HGF and its receptor c-met. Precursor cells adopt a mesenchymal morphology without losing their myogenic specification. This is achieved by the expression of the transcription factors Pax3, Pax7 and myf5. During migration, premature differentiation has to be kept at bay to enable motility and proliferation. After having reached their target sites, the dorsal and ventral myogenic zones, myogenesis is initiated by the activation of the muscle determination factors MyoD, myogenin and MRF4. Finally, we briefly summarize the process of muscle hypertrophy and regeneration during which aspects of developmental processes are reinitiated.

Research paper thumbnail of Function of Somite and Somitocoele Cells in the Formation of the Vertebral Motion Segment in Avian Embryos

Cells Tissues Organs, 1996

We have studied the distribution of thoracic somite and somitocoele-derived cells using homotopic... more We have studied the distribution of thoracic somite and somitocoele-derived cells using homotopical grafting between quail and chicken embryos and rein-cubation periods of 2-6 days. Serial sections were evaluated with antibodies against quail cells, quail hemangiopoietic cells and desmin. With the exception of neural crest cells in the cranial sclerotome half, all cells of the operated segment are quail cells derived from a single somite. These cells differentiate into sclerotome, myotome and the anlage of the dermis of the back. After longer re-incubation periods, the somite-derived quail cells form the neighboring halves of 2 adjacent vertebral bodies and the intervening (disc-homologous) tissue. Resegmentation is furthermore visible in the lamina and the spinous process. Somite cells also form the articular and transverse processes, and the intertransverse muscle including its insertion to the next cranial transverse process. One thoracic somite forms the proximal part of 1 rib. In more distal parts, 1 somite forms the cranial half of 1 rib and the caudal half of the next cranial rib, and the intercostal muscle and part of the connective tissue. Somite-derived quail cells are found in muscle that bridges over 2 segments cranial and caudal from the operated segment. The craniocaudal distribution of endothelial cells is approximately the same. Somitocoele cells that are located centrally in the epithelial somite express the sclerotome-markers Pax-1 and Pax-9. After 2-3 days of reincubation, grafted thoracic somitocoele cells are found mainly in the cranial part of the caudal sclerotome half. They form an area representing the anlagen of the intervertebral disc and the rib. After longer reincubation periods, the grafted quail somitocoele cells form the intervertebral disc-homologous tissue and the proximal part of the rib. In more distal parts of the rib they are located in the cranial half of 1 rib and the caudal half of the next cranial rib. The somitocoele cells also form the surface of the intervertebral joint, and give rise to a small number of endothelial cells that are found up to 1 segment cranial and caudal to the operation site. Our studies show that resegmentation is found in most parts of the vertebra and in the distal ribs. One somite forms the origin and insertion of the segmental muscle. Therefore, the somite can be regarded as the ancestor of the vertebral motion segment. Somitocoele cells are located centrally both in the epithelial somite and in the vertebral motion segment.

Research paper thumbnail of 1 Evolution and Development of Distinct Cell Lineages Derived from Somites

Current Topics in Developmental Biology, 1999

... There is no sharp boundary between the 36 Beate Brand-Saberi and Bodo Christ Figure 37 Whole ... more ... There is no sharp boundary between the 36 Beate Brand-Saberi and Bodo Christ Figure 37 Whole mount in situ hybridization of a 2-day chick embryo for VEGFR !I (Quek I ) (magnification: X50). ... Christ, B., Jacob, M., and Jacob, HJ (1983). On the origin and development of ...

Research paper thumbnail of Sclerotomal origin of the ribs

Research paper thumbnail of Regulation ofparaxisExpression and Somite Formation by Ectoderm- and Neural Tube-Derived Signals

Developmental Biology, May 1, 1997

During vertebrate embryogenesis, the paraxial mesoderm becomes segmented into somites, which form... more During vertebrate embryogenesis, the paraxial mesoderm becomes segmented into somites, which form as paired epithelial spheres with a periodicity that reflects the segmental organization of the embryo. As a somite matures, the ventral region gives rise to a mesenchymal cell population, the sclerotome, that forms the axial skeleton. The dorsal region of the somite remains epithelial and is called dermomyotome. The dermomyotome gives rise to the trunk and limb muscle and to the dermis of the back. Epaxial and hypaxial muscle precursors can be attributed to distinct somitic compartments which are laid down prior to overt somite differentiation. Inductive signals from the neural tube, notochord, and overlying ectoderm have been shown to be required for patterning of the somites into these different compartments. Paraxis is a basic helixloop-helix transcription factor expressed in the unsegmented paraxial mesoderm and throughout epithelial somites before becoming restricted to epithelial cells of the dermomyotome. To determine whether paraxis might be a target for inductive signals that influence somite patterning, we examined the influence of axial structures and surface ectoderm on paraxis expression by performing microsurgical operations on chick embryos. These studies revealed two distinct phases of paraxis expression, an early phase in the paraxial mesoderm that is dependent on signals from the ectoderm and independent of the neural tube, and a later phase that is supported by redundant signals from the ectoderm and neural tube. Under experimental conditions in which paraxis failed to be expressed, cells from the paraxial mesoderm failed to epithelialize and somites were not formed. We also performed an RT-PCR analysis of combined tissue explants in vitro and confirmed that surface ectoderm is sufficient to induce paraxis expression in segmental plate mesoderm. These results demonstrate that somite formation requires signals from adjacent cell types and that the paraxis gene is a target for the signal transduction pathways that regulate somitogenesis. ᭧ 1997 Academic Press Sequence data from this article have been deposited with the EMBL/GenBank Data Libraries under Accession No. U76665.

Research paper thumbnail of Kapitel 4: Kopf und Hals

Research paper thumbnail of Kapitel 10: Sinnesorgane: Auge und Ohr