Cliff Tabin

Department of Genetics
Harvard Medical School
New Research Building, 3rd Floor
77 Avenue Louis Pasteur
Boston MA 02115
Tel: (617) 432-7618
Fax: (617) 432-7595
Email: tabin@genetics.med.harvard.edu
8 postdoctoral fellows, 5 graduate students

The laboratory studies the genetic basis by which form and structure are regulated during vertebrate development. We combine classical methods of experimental embryology with modern molecular and genetic techniques for regulating gene expression during embryogenesis.

One of the classic systems for the study of embryonic development is the chick embryo, where grafting experiments have given profound insight into such questions as the patterning of developing limb axes, and the control of organogenesis. These classical experiments provide a context for interpreting modern molecular studies and the methods they employed also give us an additional set of tools for manipulating the embryo. For example, we can use retroviral vectors to alter gene expression in the context of specific transplantations or extirpations. Important complementary information is gained from studies taking advantage of the powerful techniques for regulated misexpression and gene deletion in the mouse.

The lab has major efforts underway exploiting these approaches to understand limb development, from the establishment of the initial axes, to understanding the difference in genetic controls between an arm and a leg, through later specific events such as differential bone growth and specific muscle patterning; and to understand the establishment of left-right asymmetry (e.g.. why your heart is on the left and not the right) from the initiation of the left-right difference, through signaling cascades, to left- or right-specific morphogenesis. We also currently have projects looking at the differentiation of the somites and morphogenesis of the heart, as well as biochemical analysis of the hedgehog signal transduction system, a key signaling pathway during development. In addition, we have evolutionary projects examining the developmental and genetic basis for the morphological variation seen in Darwin's Finches and in cave fish.

References:

• Hornstein, E., Mansfield, JH., Yekta, S., Hu, JK-H., Harfe, BD., McManus, M., Baskerville, S., Bartel, DP., Tabin, CJ. miR-196 upstream of Hoxb-8 and Shh in limb development. Nature, 2005, Dec;438(7068):671-674
• Harfe, BD., Scherz, PJ., Nissim, S., Tian, H., McMahon, AP. and Tabin, CJ. Evidence for an expansion-based temporal Shh gradient in specifying vertebrate digit identities. Cell 2004, August;118(4):517-528
• Abzhanov, A., Protas, M., Grant, R., Grant, P. and Tabin, CJ. Bmp4 and morphological variation of the beaks of Darwin's Finches. Science 2004, September;305(5689):1462-1465