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Neuritin: a gene induced by neural activity and neurotrophins that promotes neuritogenesis.

ABSTRACT: Neural activity and neurotrophins induce synaptic remodeling in part by altering gene expression. A cDNA encoding a glycosylphoshatidylinositol-anchored protein was identified by screening for hippocampal genes that are induced by neural activity. This molecule, named neuritin, is expressed in postmitotic-differentiating neurons of the developing nervous system and neuronal structures associated with plasticity in the adult. Neuritin message is induced by neuronal activity and by the activity-regulated neurotrophins BDNF and NT-3. Purified recombinant neuritin promotes neurite outgrowth and arborization in primary embryonic hippocampal and cortical cultures. These data implicate neuritin as a downstream effector of activity-induced neurite outgrowth.

SUBMITTER: Naeve GS

PROVIDER: S-EPMC20143 | biostudies-literature | 1997 Mar

REPOSITORIES: biostudies-literature

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Neuritin: a gene induced by neural activity and neurotrophins that promotes neuritogenesis.

Naeve G S GS Ramakrishnan M M Kramer R R Hevroni D D Citri Y Y Theill L E LE

Proceedings of the National Academy of Sciences of the United States of America 19970301 6

Neural activity and neurotrophins induce synaptic remodeling in part by altering gene expression. A cDNA encoding a glycosylphoshatidylinositol-anchored protein was identified by screening for hippocampal genes that are induced by neural activity. This molecule, named neuritin, is expressed in postmitotic-differentiating neurons of the developing nervous system and neuronal structures associated with plasticity in the adult. Neuritin message is induced by neuronal activity and by the activity-re ...[more]

PMID: 9122250

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Project description:Neuroepithelial cell (NEC) elongation is one of several key cell behaviors that mediate the tissue-level morphogenetic movements that shape the neural tube (NT), the precursor of the brain and spinal cord. However, the upstream signals that promote NEC elongation have been difficult to tease apart from those regulating apico-basal polarity and hingepoint formation, due to their confounding interdependence. The Repulsive Guidance Molecule a (Rgma)/Neogenin 1 (Neo1) signaling pathway plays a conserved role in NT formation (neurulation) and is reported to regulate both NEC elongation and apico-basal polarity, through signal transduction events that have not been identified. We examine here the role of Rgma/Neo1 signaling in zebrafish (sex unknown), an organism that does not use hingepoints to shape its hindbrain, thereby enabling a direct assessment of the role of this pathway in NEC elongation. We confirm that Rgma/Neo1 signaling is required for microtubule-mediated NEC elongation, and demonstrate via cell transplantation that Neo1 functions cell autonomously to promote elongation. However, in contrast to previous findings, our data do not support a role for this pathway in establishing apical junctional complexes. Last, we provide evidence that Rgma promotes Neo1 glycosylation and intramembrane proteolysis, resulting in the production of a transient, nuclear intracellular fragment (NeoICD). Partial rescue of Neo1a and Rgma knockdown embryos by overexpressing neoICD suggests that this proteolytic cleavage is essential for neurulation. Based on these observations, we propose that RGMA-induced NEO1 proteolysis orchestrates NT morphogenesis by promoting NEC elongation independently of the establishment of apical junctional complexes.SIGNIFICANCE STATEMENT The neural tube, the CNS precursor, is shaped during neurulation. Neural tube defects occur frequently, yet underlying genetic risk factors are poorly understood. Neuroepithelial cell (NEC) elongation is essential for proper completion of neurulation. Thus, connecting NEC elongation with the molecular pathways that control this process is expected to reveal novel neural tube defect risk factors and increase our understanding of NT development. Effectors of cell elongation include microtubules and microtubule-associated proteins; however, upstream regulators remain controversial due to the confounding interdependence of cell elongation and establishment of apico-basal polarity. Here, we reveal that Rgma-Neo1 signaling controls NEC elongation independently of the establishment of apical junctional complexes and identify Rgma-induced Neo1 proteolytic cleavage as a key upstream signaling event.

Dataset Information

Neuritin: a gene induced by neural activity and neurotrophins that promotes neuritogenesis.

Publications

Neuritin: a gene induced by neural activity and neurotrophins that promotes neuritogenesis.

Similar Datasets

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