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Herbert Hildebrandt - One of the best experts on this subject based on the ideXlab platform.
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sialic acids in the brain gangliosides and polysialic acid in Nervous System Development stability disease and regeneration
Physical Review, 2014Co-Authors: Ronald L Schnaar, Herbert Hildebrandt, Rita GerardyschahnAbstract:Every cell in nature carries a rich surface coat of glycans, its glycocalyx, which constitutes the cell's interface with its environment. In eukaryotes, the glycocalyx is composed of glycolipids, glycoproteins, and proteoglycans, the compositions of which vary among different tissues and cell types. Many of the linear and branched glycans on cell surface glycoproteins and glycolipids of vertebrates are terminated with sialic acids, nine-carbon sugars with a carboxylic acid, a glycerol side-chain, and an N-acyl group that, along with their display at the outmost end of cell surface glycans, provide for varied molecular interactions. Among their functions, sialic acids regulate cell-cell interactions, modulate the activities of their glycoprotein and glycolipid scaffolds as well as other cell surface molecules, and are receptors for pathogens and toxins. In the brain, two families of sialoglycans are of particular interest: gangliosides and polysialic acid. Gangliosides, sialylated glycosphingolipids, are the most abundant sialoglycans of nerve cells. Mouse genetic studies and human disorders of ganglioside metabolism implicate gangliosides in axon-myelin interactions, axon stability, axon regeneration, and the modulation of nerve cell excitability. Polysialic acid is a unique homopolymer that reaches >90 sialic acid residues attached to select glycoproteins, especially the neural cell adhesion molecule in the brain. Molecular, cellular, and genetic studies implicate polysialic acid in the control of cell-cell and cell-matrix interactions, intermolecular interactions at cell surfaces, and interactions with other molecules in the cellular environment. Polysialic acid is essential for appropriate brain Development, and polymorphisms in the human genes responsible for polysialic acid biosynthesis are associated with psychiatric disorders including schizophrenia, autism, and bipolar disorder. Polysialic acid also appears to play a role in adult brain plasticity, including regeneration. Together, vertebrate brain sialoglycans are key regulatory components that contribute to proper Development, maintenance, and health of the Nervous System.
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sialic acids in the brain gangliosides and polysialic acid in Nervous System Development stability disease and regeneration
Physical Review, 2014Co-Authors: Ronald L Schnaar, Herbert Hildebrandt, Rita GerardyschahnAbstract:Every cell in nature carries a rich surface coat of glycans, its glycocalyx, which constitutes the cell's interface with its environment. In eukaryotes, the glycocalyx is composed of glycolipids, g...
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sialic acids in the brain gangliosides and polysialic acid in Nervous System Development stability disease and regeneration
Physical Review, 2014Co-Authors: Ronald L Schnaar, Herbert Hildebrandt, Rita GerardyschahnAbstract:Every cell in nature carries a rich surface coat of glycans, its glycocalyx, which constitutes the cell's interface with its environment. In eukaryotes, the glycocalyx is composed of glycolipids, g...
Rita Gerardyschahn - One of the best experts on this subject based on the ideXlab platform.
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sialic acids in the brain gangliosides and polysialic acid in Nervous System Development stability disease and regeneration
Physical Review, 2014Co-Authors: Ronald L Schnaar, Herbert Hildebrandt, Rita GerardyschahnAbstract:Every cell in nature carries a rich surface coat of glycans, its glycocalyx, which constitutes the cell's interface with its environment. In eukaryotes, the glycocalyx is composed of glycolipids, glycoproteins, and proteoglycans, the compositions of which vary among different tissues and cell types. Many of the linear and branched glycans on cell surface glycoproteins and glycolipids of vertebrates are terminated with sialic acids, nine-carbon sugars with a carboxylic acid, a glycerol side-chain, and an N-acyl group that, along with their display at the outmost end of cell surface glycans, provide for varied molecular interactions. Among their functions, sialic acids regulate cell-cell interactions, modulate the activities of their glycoprotein and glycolipid scaffolds as well as other cell surface molecules, and are receptors for pathogens and toxins. In the brain, two families of sialoglycans are of particular interest: gangliosides and polysialic acid. Gangliosides, sialylated glycosphingolipids, are the most abundant sialoglycans of nerve cells. Mouse genetic studies and human disorders of ganglioside metabolism implicate gangliosides in axon-myelin interactions, axon stability, axon regeneration, and the modulation of nerve cell excitability. Polysialic acid is a unique homopolymer that reaches >90 sialic acid residues attached to select glycoproteins, especially the neural cell adhesion molecule in the brain. Molecular, cellular, and genetic studies implicate polysialic acid in the control of cell-cell and cell-matrix interactions, intermolecular interactions at cell surfaces, and interactions with other molecules in the cellular environment. Polysialic acid is essential for appropriate brain Development, and polymorphisms in the human genes responsible for polysialic acid biosynthesis are associated with psychiatric disorders including schizophrenia, autism, and bipolar disorder. Polysialic acid also appears to play a role in adult brain plasticity, including regeneration. Together, vertebrate brain sialoglycans are key regulatory components that contribute to proper Development, maintenance, and health of the Nervous System.
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sialic acids in the brain gangliosides and polysialic acid in Nervous System Development stability disease and regeneration
Physical Review, 2014Co-Authors: Ronald L Schnaar, Herbert Hildebrandt, Rita GerardyschahnAbstract:Every cell in nature carries a rich surface coat of glycans, its glycocalyx, which constitutes the cell's interface with its environment. In eukaryotes, the glycocalyx is composed of glycolipids, g...
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sialic acids in the brain gangliosides and polysialic acid in Nervous System Development stability disease and regeneration
Physical Review, 2014Co-Authors: Ronald L Schnaar, Herbert Hildebrandt, Rita GerardyschahnAbstract:Every cell in nature carries a rich surface coat of glycans, its glycocalyx, which constitutes the cell's interface with its environment. In eukaryotes, the glycocalyx is composed of glycolipids, g...
Michael Wegner - One of the best experts on this subject based on the ideXlab platform.
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soxe function in vertebrate Nervous System Development
The International Journal of Biochemistry & Cell Biology, 2010Co-Authors: Claus C Stolt, Michael WegnerAbstract:Sox8, Sox9, and Sox10 as transcription factors of subgroup E of the Sox protein family are essential for many aspects of Nervous System Development. These SoxE proteins are already required for the initial neural crest induction, but also guarantee survival and maintenance of pluripotency in migrating neural crest stem cells. SoxE proteins are furthermore key regulators of glial specification in both the peripheral and the central Nervous Systems. At later stages of Development, Sox10 plays crucial roles in Schwann cells and oligodendrocytes for terminal differentiation and myelin formation. In both glial cell types, Sox10 controls directly the expression of genes encoding the major myelin proteins. SoxE proteins are well-integrated components of regulatory networks and as such modulated in their activity by cooperating or antagonistic transcription factors such as SoxD or various bHLH proteins. The multiple functions in peripheral and central Nervous System Development also link SoxE proteins to various human diseases and identify these proteins as promising targets of future therapeutic approaches.
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replacement of the sox10 transcription factor by sox8 reveals incomplete functional equivalence
Development, 2006Co-Authors: Susanne Kellerer, Claus C Stolt, Silke Schreiner, Stefanie Scholz, Michael R Bosl, Michael WegnerAbstract:Sox8 and Sox10 are two closely related transcription factors of the Sox protein family with overlapping expression patterns during Development. They are believed to perform very similar functions because several Developmental processes, including enteric Nervous System Development and oligodendrocyte differentiation, are regulated by both Sox proteins. To analyze the extent of functional equivalence between the two Sox proteins, we employed targeted mutagenesis to replace Sox10 with Sox8 in the mouse. In mice that expressed Sox8 instead of Sox10, Sox10 deficiency was phenotypically rescued to different extents in affected tissues. Whereas Development of glial cells and neurons in the sensory and sympathetic parts of the peripheral Nervous System was almost normal when Sox10 was replaced by Sox8, melanocyte Development was as defective as in Sox10-deficient mice. The ability of Sox8 to rescue the defects in enteric Nervous System Development and oligodendrocyte differentiation of Sox10-deficient mice was limited. We conclude that the extent of functional equivalence depends on the tissue and that, despite their relatedness, Sox8 and Sox10 have more unique functions than previously appreciated.
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identification of sox8 as a modifier gene in a mouse model of hirschsprung disease reveals underlying molecular defect
Developmental Biology, 2005Co-Authors: Marzena Maka, Claus C Stolt, Michael WegnerAbstract:Mice carrying heterozygous mutations in the Sox10 gene display aganglionosis of the colon and represent a model for human Hirschsprung disease. Here, we show that the closely related Sox8 functions as a modifier gene for Sox10-dependent enteric Nervous System defects as it increases both penetrance and severity of the defect in Sox10 heterozygous mice despite having no detectable influence on enteric Nervous System Development on its own. Sox8 exhibits an expression pattern very similar to Sox10 with occurrence in vagal and enteric neural crest cells and later confinement to enteric glia. Loss of Sox8 alleles in Sox10 heterozygous mice impaired colonization of the gut by enteric neural crest cells already at early times. Whereas proliferation, apoptosis, and neuronal differentiation were normal for enteric neural crest cells in the gut of mutant mice, apoptosis was dramatically increased in vagal neural crest cells outside the gut. The defects in enteric Nervous System Development of mice with Sox10 and Sox8 mutations are therefore likely caused by a reduction of the pool of undifferentiated vagal neural crest cells. Our study suggests that Sox8 and Sox10 are jointly required for the maintenance of these vagal neural crest stem cells.
Ronald L Schnaar - One of the best experts on this subject based on the ideXlab platform.
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sialic acids in the brain gangliosides and polysialic acid in Nervous System Development stability disease and regeneration
Physical Review, 2014Co-Authors: Ronald L Schnaar, Herbert Hildebrandt, Rita GerardyschahnAbstract:Every cell in nature carries a rich surface coat of glycans, its glycocalyx, which constitutes the cell's interface with its environment. In eukaryotes, the glycocalyx is composed of glycolipids, glycoproteins, and proteoglycans, the compositions of which vary among different tissues and cell types. Many of the linear and branched glycans on cell surface glycoproteins and glycolipids of vertebrates are terminated with sialic acids, nine-carbon sugars with a carboxylic acid, a glycerol side-chain, and an N-acyl group that, along with their display at the outmost end of cell surface glycans, provide for varied molecular interactions. Among their functions, sialic acids regulate cell-cell interactions, modulate the activities of their glycoprotein and glycolipid scaffolds as well as other cell surface molecules, and are receptors for pathogens and toxins. In the brain, two families of sialoglycans are of particular interest: gangliosides and polysialic acid. Gangliosides, sialylated glycosphingolipids, are the most abundant sialoglycans of nerve cells. Mouse genetic studies and human disorders of ganglioside metabolism implicate gangliosides in axon-myelin interactions, axon stability, axon regeneration, and the modulation of nerve cell excitability. Polysialic acid is a unique homopolymer that reaches >90 sialic acid residues attached to select glycoproteins, especially the neural cell adhesion molecule in the brain. Molecular, cellular, and genetic studies implicate polysialic acid in the control of cell-cell and cell-matrix interactions, intermolecular interactions at cell surfaces, and interactions with other molecules in the cellular environment. Polysialic acid is essential for appropriate brain Development, and polymorphisms in the human genes responsible for polysialic acid biosynthesis are associated with psychiatric disorders including schizophrenia, autism, and bipolar disorder. Polysialic acid also appears to play a role in adult brain plasticity, including regeneration. Together, vertebrate brain sialoglycans are key regulatory components that contribute to proper Development, maintenance, and health of the Nervous System.
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sialic acids in the brain gangliosides and polysialic acid in Nervous System Development stability disease and regeneration
Physical Review, 2014Co-Authors: Ronald L Schnaar, Herbert Hildebrandt, Rita GerardyschahnAbstract:Every cell in nature carries a rich surface coat of glycans, its glycocalyx, which constitutes the cell's interface with its environment. In eukaryotes, the glycocalyx is composed of glycolipids, g...
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sialic acids in the brain gangliosides and polysialic acid in Nervous System Development stability disease and regeneration
Physical Review, 2014Co-Authors: Ronald L Schnaar, Herbert Hildebrandt, Rita GerardyschahnAbstract:Every cell in nature carries a rich surface coat of glycans, its glycocalyx, which constitutes the cell's interface with its environment. In eukaryotes, the glycocalyx is composed of glycolipids, g...
Elaine C Seaver - One of the best experts on this subject based on the ideXlab platform.
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functional role of pax6 during eye and Nervous System Development in the annelid capitella teleta
Developmental Biology, 2019Co-Authors: Marleen Klann, Elaine C SeaverAbstract:The transcription factor Pax6 is an important regulator of early animal Development. Loss of function mutations of pax6 in a range of animals result in a reduction or complete loss of the eye, a reduction of a subset of neurons, and defects in axon growth. There are no studies focusing on the role of pax6 during Development of any lophotrochozoan representative, however, expression of pax6 in the developing eye and Nervous System in a number of species suggest that pax6 plays a highly conserved role in eye and Nervous System formation. We investigated the functional role of pax6 during Development of the marine annelid Capitella teleta. Expression of pax6 transcripts in C. teleta larvae is similar to patterns found in other animals, with distinct subdomains in the brain and ventral nerve cord as well as in the larval and juvenile eye. To perturb pax6 function, two different splice-blocking morpholinos and a translation-blocking morpholino were used. Larvae resulting from microinjections with either splice-blocking morpholino show a reduction of the pax6 transcript. Development of both the larval eyes and the central Nervous System architecture are highly disrupted following microinjection of each of the three morpholinos. The less severe phenotype observed when only the homeodomain is disrupted suggests that presence of the paired domain is sufficient for partial function of the Pax6 protein. Preliminary downstream target analysis confirms disruption in expression of some components of the retinal gene regulatory network, as well as disruption of genes involved in Nervous System Development. Results from this study, taken together with studies from other species, reveal an evolutionarily conserved role for pax6 in eye and neural specification and Development.
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functional role of pax6 in eye and central Nervous System Development in the annelid capitella teleta
bioRxiv, 2018Co-Authors: Marleen Klann, Elaine C SeaverAbstract:The transcription factor Pax6 is an important regulator of early animal Development. Loss of function mutations of pax6 in a range of animals results in a reduction or complete loss of the eye, a reduction of a subset of neurons, and defects in axon growth. There are no studies focusing on the role of pax6 during Development of any lophotrochozoan representative, however, expression of pax6 in the developing eye and Nervous System in a number of species suggest that pax6 plays a highly conserved role in eye and Nervous System formation. We investigated the functional role of pax6 during Development of the marine annelid Capitella teleta. Expression of pax6 transcripts in C. teleta larvae is similar to patterns found in other animals, with distinct subdomains in the brain and ventral nerve cord as well as in the larval and adult eye. To perturb pax6 function, two different splice-blocking morpholinos were used. Larvae resulting from injections with either morpholino show a reduction of the pax6 transcript, and Development of both the larval eyes and the central Nervous System architecture are highly disrupted. Preliminary downstream target analysis confirms disruption in expression of some components of the retinal gene regulatory network, as well as disruption of genes involved in Nervous System Development. Results from this study, taken together with studies from other species, reveal an evolutionarily conserved role for pax6 in eye Development, and in neural specification and Development.
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spatiotemporal regulation of Nervous System Development in the annelid capitella teleta
Evodevo, 2017Co-Authors: Abhinav Sur, Craig Magie, Elaine C Seaver, Neva P MeyerAbstract:How Nervous Systems evolved remains an unresolved question. Previous studies in vertebrates and arthropods revealed that homologous genes regulate important neurogenic processes such as cell proliferation and differentiation. However, the mechanisms through which such homologs regulate neurogenesis across different bilaterian clades are variable, making inferences about Nervous System evolution difficult. A better understanding of neurogenesis in the third major bilaterian clade, Spiralia, would greatly contribute to our ability to deduce the ancestral mechanism of neurogenesis. Using whole-mount in situ hybridization, we examined spatiotemporal gene expression for homologs of soxB, musashi, prospero, achaete–scute, neurogenin, and neuroD in embryos and larvae of the spiralian annelid Capitella teleta, which has a central Nervous System (CNS) comprising a brain and ventral nerve cord. For all homologs examined, we found expression in the neuroectoderm and/or CNS during neurogenesis. Furthermore, the onset of expression and localization within the developing neural tissue for each of these genes indicates putative roles in separate phases of neurogenesis, e.g., in neural precursor cells (NPCs) versus in cells that have exited the cell cycle. Ct-soxB1, Ct-soxB, and Ct-ngn are the earliest genes expressed in surface cells in the anterior and ventral neuroectoderm, while Ct-ash1 expression initiates slightly later in surface neuroectoderm. Ct-pros is expressed in single cells in neural and non-neural ectoderm, while Ct-msi and Ct-neuroD are localized to differentiating neural cells in the brain and ventral nerve cord. These results suggest that the genes investigated in this article are involved in a neurogenic gene regulatory network in C. teleta. We propose that Ct-SoxB1, Ct-SoxB, and Ct-Ngn are involved in maintaining NPCs in a proliferative state. Ct-Pros may function in division of NPCs, Ct-Ash1 may promote cell cycle exit and ingression of NPC daughter cells, and Ct-NeuroD and Ct-Msi may control neuronal differentiation. Our results support the idea of a common genetic toolkit driving neural Development whose molecular architecture has been rearranged within and across clades during evolution. Future functional studies should help elucidate the role of these homologs during C. teleta neurogenesis and identify which aspects of bilaterian neurogenesis may have been ancestral or were derived within Spiralia.
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Spatiotemporal regulation of Nervous System Development in the annelid Capitella teleta
BMC, 2017Co-Authors: Abhinav Sur, Craig Magie, Elaine C Seaver, Neva P MeyerAbstract:Abstract Background How Nervous Systems evolved remains an unresolved question. Previous studies in vertebrates and arthropods revealed that homologous genes regulate important neurogenic processes such as cell proliferation and differentiation. However, the mechanisms through which such homologs regulate neurogenesis across different bilaterian clades are variable, making inferences about Nervous System evolution difficult. A better understanding of neurogenesis in the third major bilaterian clade, Spiralia, would greatly contribute to our ability to deduce the ancestral mechanism of neurogenesis. Results Using whole-mount in situ hybridization, we examined spatiotemporal gene expression for homologs of soxB, musashi, prospero, achaete–scute, neurogenin, and neuroD in embryos and larvae of the spiralian annelid Capitella teleta, which has a central Nervous System (CNS) comprising a brain and ventral nerve cord. For all homologs examined, we found expression in the neuroectoderm and/or CNS during neurogenesis. Furthermore, the onset of expression and localization within the developing neural tissue for each of these genes indicates putative roles in separate phases of neurogenesis, e.g., in neural precursor cells (NPCs) versus in cells that have exited the cell cycle. Ct-soxB1, Ct-soxB, and Ct-ngn are the earliest genes expressed in surface cells in the anterior and ventral neuroectoderm, while Ct-ash1 expression initiates slightly later in surface neuroectoderm. Ct-pros is expressed in single cells in neural and non-neural ectoderm, while Ct-msi and Ct-neuroD are localized to differentiating neural cells in the brain and ventral nerve cord. Conclusions These results suggest that the genes investigated in this article are involved in a neurogenic gene regulatory network in C. teleta. We propose that Ct-SoxB1, Ct-SoxB, and Ct-Ngn are involved in maintaining NPCs in a proliferative state. Ct-Pros may function in division of NPCs, Ct-Ash1 may promote cell cycle exit and ingression of NPC daughter cells, and Ct-NeuroD and Ct-Msi may control neuronal differentiation. Our results support the idea of a common genetic toolkit driving neural Development whose molecular architecture has been rearranged within and across clades during evolution. Future functional studies should help elucidate the role of these homologs during C. teleta neurogenesis and identify which aspects of bilaterian neurogenesis may have been ancestral or were derived within Spiralia
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Nervous System Development in lecithotrophic larval and juvenile stages of the annelid capitella teleta
Frontiers in Zoology, 2015Co-Authors: Neva P Meyer, Allan Carrillobaltodano, Richard E Moore, Elaine C SeaverAbstract:Background Reconstructing the evolutionary history of Nervous Systems requires an understanding of their architecture and Development across diverse taxa. The spiralians encompass diverse body plans and organ Systems, and within the spiralians, annelids exhibit a variety of morphologies, life histories, feeding modes and associated Nervous Systems, making them an ideal group for studying evolution of Nervous Systems.