Colin Jamora
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.
Jamora, C., Lee, P., Kocieniewski, P., Alonso, L., Azhar, M., Hosokawa, R., Chai, Y., Fuchs, E. (2004). A signaling pathway involving TGFß2 and Snail in hair bud morphogenesis. PLoS Biology 3(1): e11.
Jamora, C., Dasgupta, R., Kocieniewski, P., and Fuchs, E. (2003). Molecular links between signal transduction, transcription and adhesion in specifying epithelial bud development. Nature 200(422): 317-322.
Perez-Moreno, M., Jamora, C., and Fuchs, E. (2003). Sticky business – orchestrating cellular signals at adherens junctions. Cell 112(4): 535-548.
Jamora, C. and Fuchs, E. (2002). Intercellular adhesion, signaling and the cytoskeleton. Nature Cell Biology (4): E101-108.
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.
