My lab is primarily interested in early events in mammalian development and the
signalling pathways that regulated these processes. All vertebrates start as
a single cell that undergoes a series of orchestrated cell divisions to form
an embryo. During development, one of the first steps is to create a plan
for the embryonic body with anterior-posterior, dorsal-ventral, and
left-right axes.
Establishing the body plan of an embryo requires complex cell-cell
communication networks. Organizing centers have been identified in the
embryo which act as initiating sources for signaling networks and direct
surrounding cells into appropriate patterns. Two distinct organizing centers
are found in early mammalian embryos, the anterior visceral endoderm (AVE),
which is required for head structures, and the node, which coordinates the
body. How these organizers are formed and how they function to pattern the
embryo remains poorly understood.
One family of growth factors implicated in embryonic patterning is the
transforming growth factor-β (TGFβ) family. This family can be subdivided
into three classes, the TGFβs, activin/nodals and bone morphogenetic
proteins (BMPs). These extracellular ligands bind to receptors on the cell
surface that activate intracellular signalling molecules and regulate
transcription of genes in the nucleus. Research in my laboratory is focused
on understanding the functions and mechanisms through which the TGFβ family
of ligands regulates developmental processes such as embryonic patterning.
In addition to examining specific pathways, we are also using genome
approaches to examine tissue differentiation during development. In
collaboration with the Genome Science Centre
at the BC Cancer Agency, we are generating an atlas of gene expression
profiles from various tissues throughout development using serial analysis
of gene expression (SAGE). This will produce a database in which the
patterns of gene expression can be quantitatively compared between different
developmental stages of a tissue and between different tissues. Data from
our project can be viewed and downloaded from our website:
www.mouseatlas.org
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