Interactions between retinoic acid, nerve growth factor and sonic hedgehog signalling pathways in neurite outgrowth

P L So, P K Yip, S Bunting, L F Wong, N D Mazarakis, S Hall, S McMahon, M Maden, J P T Corcoran

Research output: Contribution to journalArticlepeer-review

39 Citations (Scopus)

Abstract

Many studies have shown a role of retinoid signalling in neurite outgrowth in vitro, and that the retinoic acid receptor (RAR) beta 2 is critical for this process. We show here that RAR beta 2 is expressed predominantly in dorsal root ganglia (DRG) neuronal subtypes that express neurofilament (NF) 200 and calcitonin gene-related peptide (CGRP), and that these neurons extend neurites in response to RA. We demonstrate that retinoid signalling has a role in neurite outgrowth in vivo, by showing that in a peripheral nerve crush model there is less neurite outgrowth from RARP null DRG compared to wild-type. We identify sonic hedgehog (Shh) as a downstream target of the RAR beta 2 signalling pathway as it is expressed in the injured DRG of wild-type but not RAR beta null mice. This regulation is direct as when RAR beta 2 is overexpressed in adult motoneurons Shh is induced in them. Finally we show that Shh alone cannot induce neurite outgrowth but potentiates RAR beta 2 signalling in this process. (c) 2006 Elsevier Inc. All rights reserved
Original languageEnglish
Pages (from-to)167 - 175
Number of pages9
JournalDevelopmental Biology
Volume298
Issue number1
DOIs
Publication statusPublished - 1 Oct 2006

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