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...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-03-01
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| Series: | Frontiers in Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2023.1047767/full |
| _version_ | 1797866887688749056 |
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| author | Madeline McKean Francesca R. Napoli Tahira Hasan Thea Joseph Alison Wheeler Katherine Beebe Stephanie Soriano-Cruz Minori Kawano Clinton Cave |
| author_facet | Madeline McKean Francesca R. Napoli Tahira Hasan Thea Joseph Alison Wheeler Katherine Beebe Stephanie Soriano-Cruz Minori Kawano Clinton Cave |
| author_sort | Madeline McKean |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-09T23:31:28Z |
| format | Article |
| id | doaj.art-191e3d6588514cce8a198fdef28438bd |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-04-09T23:31:28Z |
| publishDate | 2023-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-191e3d6588514cce8a198fdef28438bd2023-03-21T04:42:13ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2023-03-011710.3389/fnins.2023.10477671047767GDE6 promotes progenitor identity in the vertebrate neural tubeMadeline McKeanFrancesca R. NapoliTahira HasanThea JosephAlison WheelerKatherine BeebeStephanie Soriano-CruzMinori KawanoClinton CaveThe 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.https://www.frontiersin.org/articles/10.3389/fnins.2023.1047767/fullGDE6neural tube developmentpatterningneurogenesishyperplasia |
| spellingShingle | Madeline McKean Francesca R. Napoli Tahira Hasan Thea Joseph Alison Wheeler Katherine Beebe Stephanie Soriano-Cruz Minori Kawano Clinton Cave GDE6 promotes progenitor identity in the vertebrate neural tube Frontiers in Neuroscience GDE6 neural tube development patterning neurogenesis hyperplasia |
| 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 | GDE6 neural tube development patterning neurogenesis hyperplasia |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2023.1047767/full |
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