Lgi4 promotes the proliferation and differentiation of glial lineage cells throughout the developing peripheral nervous system

Jinsuke Nishino, Thomas L. Saunders, Koji Sagane, Sean J. Morrison

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

The mechanisms that regulate peripheral nervous system (PNS) gliogenesis are incompletely understood. For example, gut neural crest stem cells (NCSCs) do not respond to known gliogenic factors, suggesting that yet-unidentified factors regulate gut gliogenesis. To identify new mechanisms, we performed gene expression profiling to identify factors secreted by gut NCSCs during the gliogenic phase of development. These cells highly expressed leucine-rich glioma inactivated 4 (Lgi4) despite the fact that Lgi4 has never been implicated in stem cell function or enteric nervous system development. Lgi4 is known to regulate peripheral nerve myelination (having been identified as the mutated gene in spontaneously arising claw paw mutant mice), but Lgi4 is not known to play any role in PNS development outside of peripheral nerves. To systematically analyze Lgi4 function, we generated gene-targeted mice. Lgi4-deficient mice exhibited a more severe phenotype than claw paw mice and had gliogenic defects in sensory, sympathetic, and enteric ganglia. We found that Lgi4 is required for the proliferation and differentiation of glial-restricted progenitors throughout the PNS. Analysis of compound-mutant mice revealed that the mechanism by which Lgi4 promotes enteric gliogenesis involves binding the ADAM22 receptor. Our results identify a new mechanism regulating enteric gliogenesis as well as novel functions for Lgi4 regulating the proliferation and maturation of glial lineage cells throughout the PNS.

Original languageEnglish (US)
Pages (from-to)15228-15240
Number of pages13
JournalJournal of Neuroscience
Volume30
Issue number45
DOIs
StatePublished - Nov 10 2010

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Peripheral Nervous System
Leucine
Glioma
Neuroglia
proctolin
Hoof and Claw
Neural Stem Cells
Neural Crest
Peripheral Nerves
Enteric Nervous System
Sympathetic Ganglia
Gene Expression Profiling
Genes
Stem Cells
Phenotype

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Lgi4 promotes the proliferation and differentiation of glial lineage cells throughout the developing peripheral nervous system. / Nishino, Jinsuke; Saunders, Thomas L.; Sagane, Koji; Morrison, Sean J.

In: Journal of Neuroscience, Vol. 30, No. 45, 10.11.2010, p. 15228-15240.

Research output: Contribution to journalArticle

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