Properties of ectopic neurons induced by Xenopus neurogenin1 misexpression.
We have examined cells cultured from ectoderm-misexpressing Neurogenin1 (Ngn1) to describe better the extent to which this gene can control aspects of neuronal phenotype including motility, morphology, excitability, and synaptic properties. Like primary spinal neurons which normally express Ngn1, cells in Ngn1-misexpressing cultures exhibit a motility-correlated behavior called circus movements prior to neuritogenesis. Misexpression of NeuroD also causes circus movements and later neuronal differentiation. GSK3beta, which inhibits NeuroD function in vivo, blocks both Ngn1-induced and NeuroD-induced neuronal differentiation, while Notch signaling inhibits only Ngn1-induced neuronal differentiation, confirming that NeuroD is downstream of Ngn1 and insensitive to Notch inhibition. While interfering with NeuroD function in ventral ectoderm inhibits both circus movements and neuronal differentiation, such inhibition in the neural plate inhibits only neuronal differentiation, suggesting that additional factors regulate circus movements in the neural ectoderm. Ngn1-misexpressing cells extend N-tubulin-positive neurites and exhibit tetrodotoxin-sensitive action potentials. Unlike the majority of cultured spinal neurons, however, Ngn1-misexpressing cells do not respond to glutamate and do not form functional synapses with myocytes, suggesting that these cells are either like Rohon-Beard sensory neurons or are not fully differentiated.
Olson
E C
EC
Department of Biology, University of California, San Diego, California, 92093, USA. eolson@bidmc.harvard.edu
Schinder
A F
AF
Dantzker
J L
JL
Marcus
E A
EA
Spitzer
N C
NC
Harris
W A
WA
D000818:Animals; D002118:Calcium / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002454:Cell Differentiation; D002465:Cell Movement; D002478:Cells, Cultured; D002828:Choristoma / Q000235:genetics*; D004475:Ectoderm / Q000166:cytology / Q000502:physiology*; D004625:Embryo, Nonmammalian / Q000502:physiology; D005260:Female; D038362:Glycogen Synthase Kinase 3; D018257:Helix-Loop-Helix Motifs; D008297:Male; D020125:Mutation, Missense; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009422:Nervous System Diseases / Q000196:embryology / Q000235:genetics*; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D013569:Synapses / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology; D014157:Transcription Factors; D014981:Xenopus
D009419:Nerve Tissue Proteins; D014157:Transcription Factors; D013779:Tetrodotoxin; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3; D002118:Calcium