Biological Sciences

Colin Jamora Assistant Professor, Section of Cell and Developmental Biology, Adjunct Professor, Department of Medicine, UCSD e-mail: cjamora@biomail.ucsd.edu

     The formation of mammalian organs employs complex interactions of signaling networks that guide morphogenetic movements. To simplify these complexities, organogenesis can be deconstructed into simple “morphometric modules”(distinct intermediary structures). A recurring theme in the initial development of organs and limbs is the formation of a cluster of cells from a sheet of multipotent cells into a bud. Following this budding morphogenesis is an orchestrated program of growth including branching and/or tube formation that results in the mature organ. We currently use hair bud morphogenesis as a model system to investigate how extracellular signals coordinate changes in gene expression with contemporaneous alterations in the physical and structural characteristics of the cell to form a relatively simple looking structure. A number of signals are exchanged between the epidermal ectoderm and the underlying mesenchyme to initiate and guide hair follicle growth (Fig. 1). However, their downstream effects, both individually and in concert with each other, have yet to be comprehensively defined.

    Since the dynamic expression of epithelial (E)-cadherin is critical to morphogenesis and tissue differentiation, we focused on understanding the regulation and downstream signaling effects of this protein on hair bud development. E-cadherin forms the transmembrane core of structures that mediate intercellular adhesion known as adherens junctions (AJs) and thereby promotes the assembly of macromolecular complexes that provides cytoskeletal stability as well as intracellular signals that influence cellular behavior (Jamora and Fuchs 2002). This dual role in both adhesion and signaling explains how E-cadherin impacts upon a number of cellular parameters including cell shape, proliferation, polarity and motility. Interestingly these are the same processes that we analyze in the context of hair bud development. We previously uncovered how the simultaneous receipt of two extracellular signals (Wnt and Noggin) lead to the formation of a Lef1/ßcatenin transcription complex to downregulate E-cadherin which is a prerequisite for hair formation (Figure 2).

     We are now focusing on the downstream effects of adhesion dynamics on bud formation. In other words, where do AJ-associated proteins go and what do they do when E-cadherin levels are reduced and AJs are dissolved (Figure 3)? We also continue to systematically wade through the myriad of morphogens that direct bud formation in order to elucidate their subcellular effects as well as to understand how they work in concert with each other to form the signaling network that guides hair growth (Jamora et al., 2004). To address these questions we employ mouse genetics to determine the developmental process in which a protein of interest is participating. In combination with cell biological and biochemical techniques in primary keratinocytes we can elucidate the signaling pathways that underlie these developmental processes.

    Dr. Jamora completed his PhD at UCSD. He then carried out postdoctoral work at the University of Chicago and Rockefeller University as a fellow of the Howard Hughes Medical Institute and the Helen Hay Whitney Foundation.