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Science 329 (5991): 562-565

Copyright © 2010 by the American Association for the Advancement of Science

Btbd7 Regulates Epithelial Cell Dynamics and Branching Morphogenesis

Tomohiro Onodera,1,* Takayoshi Sakai,1,2,*,{dagger} Jeff Chi-feng Hsu,1,* Kazue Matsumoto,1 John A. Chiorini,3 Kenneth M. Yamada1,{dagger}

Abstract: During embryonic development, many organs form by extensive branching of epithelia through the formation of clefts and buds. In cleft formation, buds are delineated by the conversion of epithelial cell-cell adhesions to cell-matrix adhesions, but the mechanisms of cleft formation are not clear. We have identified Btbd7 as a dynamic regulator of branching morphogenesis. Btbd7 provides a mechanistic link between the extracellular matrix and cleft propagation through its highly focal expression leading to local regulation of Snail2 (Slug), E-cadherin, and epithelial cell motility. Inhibition experiments show that Btbd7 is required for branching of embryonic mammalian salivary glands and lungs. Hence, Btbd7 is a regulatory gene that promotes epithelial tissue remodeling and formation of branched organs.

1 Laboratory of Cell and Developmental Biology, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892–4370, USA.
2 Department of Oral-Facial Disorders, Osaka University Graduate School of Dentistry, Yamadaoka, Suita, Osaka 565-0871, Japan.
3 Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892–4370, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: sakai{at}dent.osaka-u.ac.jp (T.S.); kyamada{at}mail.nih.gov (K.M.Y.)


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