QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online 30 November 2006
doi: 10.1242/dev.02622

This Article Figures Only Full Text Full Text (PDF) Supplementary Material All Versions of this Article: dev.02622v1 134/1/85    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hasson, P. Articles by Logan, M. P. O. Search for Related Content PubMed PubMed Citation Articles by Hasson, P. Articles by Logan, M. P. O.

Tbx5 is dispensable for forelimb outgrowth

Division of Developmental Biology, MRC-National Institute for Medical Research, Mill Hill, London NW7 1AA, UK.

^* Author for correspondence (e-mail: mlogan{at}nimr.mrc.ac.uk)

Accepted 8 September 2006

Tbx5 is essential for initiation of the forelimb, and its deletion in mice results in the failure of forelimb formation. Misexpression of dominant-negative forms of Tbx5 results in limb truncations, suggesting Tbx5 is also required for forelimb outgrowth. Here we show that Tbx5 is expressed throughout the limb mesenchyme in progenitors of cartilage, tendon and muscle. Using a tamoxifeninducible Cre transgenic line, we map the time frame during which Tbx5 is required for limb development. We show that deletion of Tbx5 subsequent to limb initiation does not impair limb outgrowth. Furthermore, we distinguish two distinct phases of limb development: a Tbx5-dependent limb initiation phase, followed by a Tbx5-independent limb outgrowth phase. In humans, mutations in the T-box transcription factor TBX5 are associated with the dominant disorder Holt-Oram syndrome (HOS), which is characterised by malformations in the forelimb and heart. Our results demonstrate a short temporal requirement for Tbx5 during early limb development, and suggest that the defects found in HOS arise as a result of disrupted TBX5 function during this narrow time window.

Key words: Tbx5, Holt-Oram syndrome (HOS), Limb initiation, Limb outgrowth, Prx1CreERT2

This article has been cited by other articles:

				L. A. Naiche and V. E. Papaioannou Tbx4 is not required for hindlimb identity or post-bud hindlimb outgrowth Development, January 1, 2007; 134(1): 93 - 103. [Abstract] [Full Text] [PDF]