RGMa inhibits neurite outgrowth of neuronal progenitors from murine enteric nervous system via the neogenin receptor in vitro.
The enteric nervous system (ENS) in vertebrate embryos is formed by neural crest-derived cells. During development, these cells undergo extensive migration from the vagal and sacral regions to colonize the entire gut, where they differentiate into neurons and glial cells. Guidance molecules like netrins, semaphorins, slits, and ephrins are known to be involved in neuronal migration and axon guidance. In the CNS, the repulsive guidance molecule (RGMa) has been implicated in neuronal differentiation, migration, and apoptosis. Recently, we described the expression of the subtypes RGMa and RGMb and their receptor neogenin during murine gut development. In the present study, we investigated the influence of RGMa on neurosphere cultures derived from fetal ENS. In functional in vitro assays, RGMa strongly inhibited neurite outgrowth of differentiating progenitors via the receptor neogenin. The repulsive effect of RGMa on processes of differentiated enteric neural progenitors could be demonstrated by collapse assay. The influence of the RGM receptor on ENS was also analyzed in neogenin knockout mice. In the adult large intestine of mutants we observed disturbed ganglia formation in the myenteric plexus. Our data indicate that RGMa may be involved in differentiation processes of enteric neurons in the murine gut.
Metzger
Marco
M
Institute of Anatomy, Centre for Regenerative Medicine, University of Tuebingen, Tuebingen, Germany.
Conrad
Sabine
S
Skutella
Thomas
T
Just
Lothar
L
D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D001973:Bromodeoxyuridine / Q000494:pharmacology; D049109:Cell Proliferation; D017615:Enteric Nervous System / Q000166:cytology* / Q000254:growth & development*; D005260:Female; D058851:GPI-Linked Proteins / Q000494:pharmacology; D057809:HEK293 Cells; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007422:Intestines / Q000166:cytology / Q000294:innervation; D008565:Membrane Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D058953:Neural Stem Cells / Q000187:drug effects*; D016501:Neurites / Q000187:drug effects*; D009457:Neuroglia / Q000502:physiology; D009474:Neurons / Q000502:physiology; D011247:Pregnancy; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000963:Antimetabolites; D058851:GPI-Linked Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011956:Receptors, Cell Surface; C483496:Rgma protein, mouse; C091279:neogenin; D012313:RNA; D001973:Bromodeoxyuridine