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GDE6 promotes progenitor identity in the vertebrate neural tube

The generation of neurons in the central nervous system is a complex, stepwise process necessitating the coordinated activity of mitotic progenitors known as radial glia. Following neural tube closure, radial glia undergo a period of active proliferation to rapidly expand their population, creating...

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Autores principales: McKean, Madeline, Napoli, Francesca R., Hasan, Tahira, Joseph, Thea, Wheeler, Alison, Beebe, Katherine, Soriano-Cruz, Stephanie, Kawano, Minori, Cave, Clinton
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10070723/
https://www.ncbi.nlm.nih.gov/pubmed/37025379
http://dx.doi.org/10.3389/fnins.2023.1047767
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author McKean, Madeline
Napoli, Francesca R.
Hasan, Tahira
Joseph, Thea
Wheeler, Alison
Beebe, Katherine
Soriano-Cruz, Stephanie
Kawano, Minori
Cave, Clinton
author_facet McKean, Madeline
Napoli, Francesca R.
Hasan, Tahira
Joseph, Thea
Wheeler, Alison
Beebe, Katherine
Soriano-Cruz, Stephanie
Kawano, Minori
Cave, Clinton
author_sort McKean, Madeline
collection PubMed
description The generation of neurons in the central nervous system is a complex, stepwise process necessitating the coordinated activity of mitotic progenitors known as radial glia. Following neural tube closure, radial glia undergo a period of active proliferation to rapidly expand their population, creating a densely packed neurepithelium. Simultaneously, radial glia positioned across the neural tube are uniquely specified to produce diverse neuronal sub-types. Although these cellular dynamics are well studied, the molecular mechanisms governing them are poorly understood. The six-transmembrane Glycerophosphodiester Phosphodiesterase proteins (GDE2, GDE3, and GDE6) comprise a family of cell-surface enzymes expressed in the embryonic nervous system. GDE proteins can release Glycosylphosphatidylinositol-anchored proteins from the cell surface via cleavage of their lipid anchor. GDE2 has established roles in motor neuron differentiation and oligodendrocyte maturation, and GDE3 regulates oligodendrocyte precursor cell proliferation. Here, we describe a role for GDE6 in early neural tube development. Using RNAscope, we show that Gde6 mRNA is expressed by ventricular zone progenitors in the caudal neural tube. Utilizing in-ovo electroporation, we show that GDE6 overexpression promotes neural tube hyperplasia and ectopic growths of the neurepithelium. At later stages, electroporated embryos exhibit an expansion of the ventral patterning domains accompanied by reduced cross-repression. Ultimately, electroporated embryos fail to produce the full complement of post-mitotic motor neurons. Our findings indicate that GDE6 overexpression significantly affects radial glia function and positions GDE6 as a complementary factor to GDE2 during neurogenesis.
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spelling pubmed-100707232023-04-05 GDE6 promotes progenitor identity in the vertebrate neural tube McKean, Madeline Napoli, Francesca R. Hasan, Tahira Joseph, Thea Wheeler, Alison Beebe, Katherine Soriano-Cruz, Stephanie Kawano, Minori Cave, Clinton Front Neurosci Neuroscience The generation of neurons in the central nervous system is a complex, stepwise process necessitating the coordinated activity of mitotic progenitors known as radial glia. Following neural tube closure, radial glia undergo a period of active proliferation to rapidly expand their population, creating a densely packed neurepithelium. Simultaneously, radial glia positioned across the neural tube are uniquely specified to produce diverse neuronal sub-types. Although these cellular dynamics are well studied, the molecular mechanisms governing them are poorly understood. The six-transmembrane Glycerophosphodiester Phosphodiesterase proteins (GDE2, GDE3, and GDE6) comprise a family of cell-surface enzymes expressed in the embryonic nervous system. GDE proteins can release Glycosylphosphatidylinositol-anchored proteins from the cell surface via cleavage of their lipid anchor. GDE2 has established roles in motor neuron differentiation and oligodendrocyte maturation, and GDE3 regulates oligodendrocyte precursor cell proliferation. Here, we describe a role for GDE6 in early neural tube development. Using RNAscope, we show that Gde6 mRNA is expressed by ventricular zone progenitors in the caudal neural tube. Utilizing in-ovo electroporation, we show that GDE6 overexpression promotes neural tube hyperplasia and ectopic growths of the neurepithelium. At later stages, electroporated embryos exhibit an expansion of the ventral patterning domains accompanied by reduced cross-repression. Ultimately, electroporated embryos fail to produce the full complement of post-mitotic motor neurons. Our findings indicate that GDE6 overexpression significantly affects radial glia function and positions GDE6 as a complementary factor to GDE2 during neurogenesis. Frontiers Media S.A. 2023-03-21 /pmc/articles/PMC10070723/ /pubmed/37025379 http://dx.doi.org/10.3389/fnins.2023.1047767 Text en Copyright © 2023 McKean, Napoli, Hasan, Joseph, Wheeler, Beebe, Soriano-Cruz, Kawano and Cave. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
McKean, Madeline
Napoli, Francesca R.
Hasan, Tahira
Joseph, Thea
Wheeler, Alison
Beebe, Katherine
Soriano-Cruz, Stephanie
Kawano, Minori
Cave, Clinton
GDE6 promotes progenitor identity in the vertebrate neural tube
title GDE6 promotes progenitor identity in the vertebrate neural tube
title_full GDE6 promotes progenitor identity in the vertebrate neural tube
title_fullStr GDE6 promotes progenitor identity in the vertebrate neural tube
title_full_unstemmed GDE6 promotes progenitor identity in the vertebrate neural tube
title_short GDE6 promotes progenitor identity in the vertebrate neural tube
title_sort gde6 promotes progenitor identity in the vertebrate neural tube
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10070723/
https://www.ncbi.nlm.nih.gov/pubmed/37025379
http://dx.doi.org/10.3389/fnins.2023.1047767
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