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Tbx5 is required for forelimb bud formation and continued outgrowth

Rallis, Charalampos and Bruneau, Benoit G and Del Buono, Jo and Seidman, Christine E and Seidman, JG and Nissim, Sahar and Tabin, Clifford J and Logan, Malcolm PO (2003) 'Tbx5 is required for forelimb bud formation and continued outgrowth.' Development, 130 (12). pp. 2741-2751. ISSN 0950-1991

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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.

Item Type: Article
Uncontrolled Keywords: limb development; limb-type identity; Tbx5; T-box genes; mouse; chick
Divisions: Faculty of Science and Health
Faculty of Science and Health > Life Sciences, School of
SWORD Depositor: Elements
Depositing User: Elements
Date Deposited: 18 Jun 2021 13:56
Last Modified: 06 Jan 2022 14:10
URI: http://repository.essex.ac.uk/id/eprint/26733

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