Research

I am interested in understanding the genetic programs that underlie development and evolution of axial tissues in vertebrates. 

All axial structures, which include the bones, muscles and connective tissues of the vertebral column and ribs, develop from embryonic structures called somites.

Early in development, pairs of somites arise as balls of undifferentiated cells that flank the developing spinal cord in a regular array from the head to the tail of the embryo.  As development proceeds, each pair of somites gives rise to one vertebral motion segment, complete with bone, muscle, and connective tissue.

Each somite forms in an identical manner, driven by a well-characterized and conserved genetic mechanism.  However, each differentiates with unique morphology depending on its place along the body axis. Thus, for example, neck vertebrae are shaped quite differently from trunk vertebrae, which in turn differ from those in the pelvis or tail.

I am interested in understanding how such morphological differences arise both within and across vertebrate species, and in understanding genetic changes that underlie the evolution of the axial skeleton in birds and mammals.

Research in my lab combines experimental embryology with molecular genetic methods, primarily in chicken and mouse embryos, to examine how early patterning genes, including Hox genes, intersect with and influence genetic pathways that direct the differentiation of axial tissues.

Representative Publications

Mansfield, J.H., Harfe, B.D., Nissen, R., Obenauer, J., Srineel, J., Chaudhuri, A., Farzan-Kashani, R., Zuker, M., Pasquinelli, A., Ruvkun, G., Sharp, P.A., Tabin, C.J., McManus, M.T. (2004).  microRNA-responsive “sensor” transgenes uncover Hox-like and other developmentally regulated patterns of vertebrate microRNA expression.  Nature Genetics 36: 1079-83.

Hornstein, E., Mansfield, J.H., Hu, J., Yekta, S., Harfe, B.D., McManus, M.T., Baskerville, S., Bartel, D.P. and Tabin, C.J.  (2005).  miR-196 acts upstream of Hoxb-8 and Sonic Hedgehog in limb development.   Nature 438:  671-674.