Transmembrane protein GDE2 induces motor neuron differentiation in vivo.
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.
Rao
Meenakshi
M
Department of Neuroscience, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.
Sockanathan
Shanthini
S
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D020134:Catalytic Domain; D002453:Cell Cycle; D002454:Cell Differentiation; D002642:Chick Embryo; D018274:Electroporation; D020868:Gene Silencing; D018398:Homeodomain Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D008938:Mitosis; D008969:Molecular Sequence Data; D009046:Motor Neurons / Q000166:cytology* / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010727:Phosphoric Diester Hydrolases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering; D015398:Signal Transduction; D013116:Spinal Cord / Q000166:cytology* / Q000196:embryology / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014162:Transfection; D014212:Tretinoin / Q000378:metabolism; D014801:Vitamin A / Q000494:pharmacology
D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D010727:Phosphoric Diester Hydrolases; D034741:RNA, Small Interfering; D014157:Transcription Factors; D014212:Tretinoin; D014801:Vitamin A; C038133:glycerophosphodiester phosphodiesterase