Cell migration is essential for a variety of biological events including embryonic development, wound healing, inflammation and the metastasis of malignant cells. Our long-term goal is to understand the molecular mechanisms by which cell migration is regulated during these biological events. We focus on a family of cell surface receptors called integrins, which play critical roles in attaching cells to a substratum on which they migrate. One member of the integrin family, alpha4beta1 (a4b1) integrin, is specifically expressed in migratory cells during embryonic development. Our studies on mouse embryos deficient in the a4 integrin subunit revealed key roles of a4b1 integrin in the migration of epicardial progenitor cells on the heart and the distribution of vascular smooth muscle progenitor cells along developing blood vessels. Work is in progress to elucidate how ƒÑ4ƒÒ1 regulates the motility of these cells.

By expressing a4b1 integrin in cultured cells, we have demonstrated that this integrin promotes directionally persistent cell migration via molecular interactions at the cytoplasmic domain of the a4 integrin subunit. Work is in progress to identify the intracellular signaling components that are downstream of a4b1 and understand how this cell adhesion receptor regulates directionally persistent cell migration.

Publications:

Grazioli, A, Alves, C.S., Konstantopoulos, K and Yang, J.T. (2006). Defective blood vessel development and pericyte/pvSMC distribution in alpha 4 integrin-deficient mouse embryos. Dev. Biol. 393,165-177.

Pinco, K. A., He W., and Yang, J. T. (2002). a4b1 integrin regulates lamellipodia protrusion via a focal complex/focal adhesion-independent mechanism. Mol. Biol. Cell 13, 3203-3217.
PubMed Reference

Sengbusch, J.K., He W., Pinco, K.A. and Yang, J.T. (2002). Dual functions of a4b1 integrin in epicardial development: initial migration and long term attachment. J. Cell Biol.157, 873-882.
PubMed Reference

Pinco, K.A., Liu, S. and Yang, J.T. (2001). a4 integrin is expressed in a subset of cranial neural crest cells and in epicardial progenitor cells during early mouse development. Mech. Dev. 100, 99-103.
PubMed Reference