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First published online 11 February 2009
doi: 10.1242/dev.034025

Development 136, 933-942 (2009)
Published by The Company of Biologists 2009
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DNA binding-dependent and -independent functions of the Hand2 transcription factor during mouse embryogenesis

Ning Liu1, Ana C. Barbosa1, Shelby L. Chapman1, Svetlana Bezprozvannaya1, Xiaoxia Qi1, James A. Richardson2, Hiromi Yanagisawa1 and Eric N. Olson1,*

1 Department of Molecular Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390-9148, USA.
2 Department of Pathology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390-9148, USA.

* Author for correspondence (e-mail: eric.olson{at}utsouthwestern.edu)

Accepted 13 January 2009

The basic helix-loop-helix (bHLH) transcription factor Hand2 is required for growth and development of the heart, branchial arches and limb buds. To determine whether DNA binding is required for Hand2 to regulate the growth and development of these different embryonic tissues, we generated mutant mice in which the Hand2 locus was modified by a mutation (referred to as Hand2EDE) that abolished the DNA-binding activity of Hand2, leaving the remainder of the protein intact. In contrast to Hand2 null embryos, which display right ventricular hypoplasia and vascular abnormalities, causing severe growth retardation by E9.5 and death by E10.5, early development of the heart appeared remarkably normal in homozygous Hand2EDE mutant embryos. These mutant embryos also lacked the early defects in growth of the branchial arches seen in Hand2 null embryos and survived up to 2 to 3 days longer than did Hand2 null embryos. However, Hand2EDE mutant embryos exhibited growth defects in the limb buds similar to those of Hand2 null embryos. These findings suggest that Hand2 regulates tissue growth and development in vivo through DNA binding-dependent and -independent mechanisms.

Key words: bHLH, Hand2, Heart development, Limb development, Craniofacial development


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