A developmental role for the heterotrimeric G protein Goα in a migratory population of embryonic neurons

A. M. Horgan, M. T. Lagrange, P. F. Copenhaver

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

The heterotrimeric G proteins are an extended family of guanyl nucleotide-binding proteins that serve essential functions in the mature nervous system but whose contributions to neuronal development remain poorly understood. We have investigated the potential role of one specific G protein Goα, in the control of neuronal migration. During embryogenesis of the moth, Manduca sexta, an identified population of undifferentiated neurons (the EP cells) migrate along sets of visceral muscle bands to form part of the enteric nervous system. Previously, immunohistochemical studies indicated the presence of Correlated proteins in the EP cells during migration. We have now verified this result, using probes derived from the Goα gene in Manduca. A clone containing the full-length coding domain for Goα was sequenced from a Manduca cDNA library; digoxigenin-labeled probes were then made from this clone and used to examine the developmental expression of the Goα gene during embryogenesis. Goα-specific transcripts could first be detected in the EP cells several hours before the onset of their migration. The level of Goα expression in all of the EP cells continued to increase during migration, but subsequently was down-regulated in a subset of the postmigratory neurons at the time of their terminal differentiation. This pattern of regulated expression is consistent with the distribution of Goα-related protein in the EP cells. We also used a semi-intact culture preparation of staged embryos to investigate the effects of G protein-specific toxins on the migratory process. Intracellular injections of the wasp toxin mastoparan, a specific activator of Goα- and Goα-related proteins, inhibited the migration of individual EP cells. Injections of pertussis toxin (an inhibitor of Goα and Goα)or cholera toxin (a selective activator of Goα) had no effect on migration, although pertussis toxin treatments did cause a measurable increase in the subsequent outgrowth of axonal processes. However, co-injection of mastoparan with pertussis toxin blocked the inhibitory effects of mastoparan alone. These results suggest that Goα-coupled signaling events within the EP cells may down-regulate their migratory behavior, possibly in response to inhibitory cues that normally guide migration in the developing embryo.

Original languageEnglish (US)
Pages (from-to)640-653
Number of pages14
JournalDevelopmental Biology
Volume172
Issue number2
DOIs
StatePublished - 1995

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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