Transmembrane Protein GDE2 Induces Motor Neuron Differentiation in Vivo
Abstract
During neural development, coordinate regulation of cell-cycle exit and differentiation is essential for cell-fate specification, cell survival, and proper wiring of neuronal circuits. However, the molecules that direct these events remain poorly defined. In the developing spinal cord, the differentiation of motor neuron progenitors into postmitotic motor neurons is regulated by retinoid signaling. Here, we identify a retinoid-inducible gene, GDE2 (glycerophosphodiester phosphodiesterase 2), encoding a six-transmembrane protein that is necessary and sufficient to drive spinal motor neuron differentiation in vivo. A single amino acid mutation in the extracellular catalytic domain abolishes protein function. This reveals a critical role for glycerophosphodiester metabolism in motor neuron differentiation.
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GDE2 is one of three known GPI-anchor cleaving enzymes in vertebrates and the only one expressed in neurons.
“GDE2 is one of three known GPI-anchor cleaving enzymes in vertebrates that function at the cell surface, and the only one expressed in neurons (22–26).”
From GDE2-RECK controls ADAM10 α-secretase–mediated cleavage of amyloid precursor protein (2021) · cites this paper as [23]
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Vertebrate neurogenesis is counteracted by Sox1–3 activity
Bylund, M., Andersson, E., Novitch, B. G., & Muhr, J. (2003) · Nature Neuroscience · doi:10.1038/nn1131 · Cited by 825 · see citing works
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Pendleton, A. L., Shen, F., Taravella, A. M., Emery, S., Veeramah, K. R., Boyko, A. R., & Kidd, J. M. (2018) · BMC Biology · doi:10.1186/s12915-018-0535-2 · Cited by 156 · see citing works
GDE2 Regulates Subtype-Specific Motor Neuron Generation through Inhibition of Notch Signaling
Sabharwal, P., Lee, C., Park, S., Rao, M., & Sockanathan, S. (2011) · Neuron · doi:10.1016/j.neuron.2011.07.028 · Cited by 54 · see citing works
Self-citationGDE2-RECK controls ADAM10 α-secretase–mediated cleavage of amyloid precursor protein
Nakamura, M., Li, Y., Choi, B.-R., Matas-Rico, E., Troncoso, J., Takahashi, C., & Sockanathan, S. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.abe6178 · Cited by 38 · see citing works
Self-citationChoi, J., Park, S., & Sockanathan, S. (2014) · Development · doi:10.1242/dev.104505 · Cited by 19 · see citing works
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- Authors
- Rao, M., & Sockanathan, S.
- Affiliations
- Johns Hopkins University (US)
- Corresponding author
- Sockanathan, Shanthini
- Venue
- Science
- Published
- 2005-09-30
- Volume
- 309
- Issue
- 5744
- Pages
- 2212-2215
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2083289939
- Cited by
- 83
- References
- 1
- Citations by year
- 2025: 3 · 2024: 5 · 2023: 2 · 2022: 2 · 2021: 2 · 2020: 5 · 2019: 2 · 2018: 1 · 2017: 5 · 2016: 6 · 2015: 3 · 2014: 3 · 2013: 7 · 2012: 4
- FWCI
- 1.50
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
- Keywords
- motor neuron differentiation, retinoid signaling, spinal cord development, motor neuron progenitors, cell cycle exit, cell fate specification
- MeSH terms
- Amino Acid Sequence, Animals, Cell Cycle, Cell Differentiation, Chick Embryo, Immunohistochemistry, Mitosis, Molecular Sequence Data, Motor Neurons, Nerve Tissue Proteins, Phosphoric Diester Hydrolases, Spinal Cord, Stem Cells, Transcription Factors, Transfection, Tretinoin, Vitamin A, Signal Transduction, Electroporation, Homeodomain Proteins, Amino Acid Substitution, Catalytic Domain, Gene Silencing, RNA, Small Interfering, Basic Helix-Loop-Helix Proteins, Basic Helix-Loop-Helix Transcription Factors
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