JANET C. SHAMBAUGH

Research Interests: Differentiation, morphogenesis, and pattern

formation in the vertebrate limb.

Research In Progress:

Using the embryonic mouse or chick limb bud as model systems, many diverse developmental questions can be approached.  Starting with an interaction between two cell layers, the limb bud grows out, cells differentiate into specific tissues, and a pattern of skeletal elements is laid down in a cartilage model.  The same processes reoccur in lower animals during regeneration of limbs.  One approach to understanding these processes involves in vitro culturing of limb bud cells in conditions that allow differentiation into cartilage cells.  The sequence of molecular events that leads a cell into the cartilage pathway begins when transcription factors that specify the cartilage phenotype are placed into action.  These factors and the cascade of subsequent events are becoming better understood in recent years.

Another approach to studying limb development uses mutations that are natural or created.  Gene targeting creates mutations in known genes and gene trapping creates mutations in novel genes.  Novel genes expressed in developing limb buds can be cloned and sequenced when tagged by the gene trap construct.  The mutations are carried in cell lines, but can be introduced into very early embryos to determine the function during embryogenesis.  One such gene trap expressed in cartilage and the nervous system is currently being characterized.

Representative Student Independent Research Projects:

Sahyoun, Cyril                   PPAR-delta:  a possible downstream target of the

transcriptional corepressor, CtBP2, in Mus musculus

Trustman, Adrienne            Expression of a novel mouse gene in developing limb

bud

Gensheimer, Jennifer           Effects of retinoic acid on embryonic chick limb

bud chondrogenesis.

Representative Posters or Publications:

Shambaugh, J.C. and M. R. Lundeberg*, (2006) mCTBP2 Is Expressed at Developing Joints in Murine Limb, Abstract for poster presentation at the annual meeting of the American Society for Developmental Biology, June 17-21, University of Michigan, Ann Arbor

Shambaugh, J., A. Trustman, T. Ridolfi, M.K. Wagner, and G.E. Lyons (1999).  mCtBP2 is essential for normal limb and cardiovascular development.  Abstract for poster presentation at the annual meeting of the Society for Developmental Biology, University of Virginia, Charlottesville, VA

Baker, R. K., M.A. Haendel, B.J. Swanson, J.C. Shambaugh, B.K. Micales and G.E. Lyons (1997).  In vitro preselection of gene-trapped embryonic stem cell clones for

characterizing novel developmentally regulated genes in the mouse.  Develop. Biol.

185:  201-214.