Tbx5 is required for forelimb bud formation and continued outgrowth

Article


Rallis, C. 2003. Tbx5 is required for forelimb bud formation and continued outgrowth. Development. 130 (12), pp. 2741-2751. https://doi.org/10.1242/dev.00473
AuthorsRallis, C.
Abstract

Tbx5 is a T-box transcription factor expressed exclusively in the developing forelimb but not in the developing hindlimb of vertebrates. Tbx5 is first detected in the prospective forelimb mesenchyme prior to overt limb bud outgrowth and its expression is maintained throughout later limb development stages. Direct evidence for a role of Tbx5 in forelimb development was provided by the discovery that mutations in human TBX5 cause Holt-Oram Syndrome (HOS), a dominant disorder characterised predominantly by upper(fore) limb defects and heart abnormalities. Misexpression studies in the chick have demonstrated a role for this gene in limb-type specification. Using a conditional knockout strategy in the mouse to delete Tbx5 gene function in the developing forelimb, we demonstrate that this gene is also required at early limb bud stages for forelimb bud development. In addition, by misexpressing dominant-negative and dominant-activated forms of Tbx5 in the chick wing we provide evidence that this gene is also required at later stages of limb bud development for continued limb outgrowth. Our results provide a context to understand the defects observed in HOS caused by haploinsufficiency of TBX5 in human. Moreover, our results also demonstrate that limb bud outgrowth and specification of limb identity are linked by a requirement for Tbx5.

JournalDevelopment
Journal citation130 (12), pp. 2741-2751
ISSN09501991
Year2003
PublisherCompany of Biologists
Publisher's version
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Digital Object Identifier (DOI)https://doi.org/10.1242/dev.00473
Web address (URL)https://doi.org/10.1242/dev.00473
Publication dates
Online15 Jun 2003
Publication process dates
Deposited13 Feb 2018
Accepted10 Mar 2003
Accepted10 Mar 2003
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