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Neuropilin 1 signaling guides neural crest cells to coordinate pathway choice with cell specification

Schwarz, Q; Maden, CH; Vieira, JM; Ruhrberg, C; (2009) Neuropilin 1 signaling guides neural crest cells to coordinate pathway choice with cell specification. P NATL ACAD SCI USA , 106 (15) 6164 - 6169. 10.1073/pnas.0811521106. Green open access

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Abstract

Neural crest cells (NCCs) are highly motile embryonic stem cells that delaminate from the neuroectoderm early during vertebrate embryogenesis and differentiate at defined target sites into various essential cell types. To reach their targets, NCCs follow 1 of 3 sequential pathways that correlate with NCC fate. The firstborn NCCs travel ventrally alongside intersomitic blood vessels to form sympathetic neuronal progenitors near the dorsal aorta, while the lastborn NCCs migrate superficially beneath the epidermis to give rise to melanocytes. Yet, most NCCs enter the somites to form the intermediate wave that gives rise to sympathetic and sensory neurons. Here we show that the repulsive guidance cue SEMA3A and its receptor neuropilin 1 (NRP1) are essential to direct the intermediate wave NCC precursors of peripheral neurons from a default pathway alongside intersomitic blood vessels into the anterior sclerotome. Thus, loss of function for either gene caused excessive intersomitic NCC migration, and this led to ectopic neuronal differentiation along both the anteroposterior and dorsoventral axes of the trunk. The choice of migratory pathway did not affect the specification of NCCs, as they retained their commitment to differentiate into sympathetic or sensory neurons, even when they migrated on an ectopic dorsolateral path that is normally taken by melanocyte precursors. We conclude that NRP1 signaling coordinates pathway choice with NCC fate and therefore confines neuronal differentiation to appropriate locations.

Type: Article
Title: Neuropilin 1 signaling guides neural crest cells to coordinate pathway choice with cell specification
Open access status: An open access version is available from UCL Discovery
DOI: 10.1073/pnas.0811521106
Publisher version: http://www.ncbi.nlm.nih.gov/pmc/ articles/PMC26613...
Keywords: semaphorin, sensory neuron, sympathetic neuron, peripheral nervous system, PERIPHERAL-NERVE PROJECTION, CHICK-EMBRYO, SYMPATHETIC NEURONS, DORSOLATERAL PATH, SEMAPHORIN-III, STEM-CELLS, MIGRATION, TRUNK, DIFFERENTIATION, EXPRESSION
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
URI: https://discovery.ucl.ac.uk/id/eprint/16374
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