Brigid Hogan, Cell Biology

The development of the vertebrate embryo is a triumph of persuasion over cell autonomy. At every stage, from the establishment of the primary body plan to the elaboration of complex organs from simple primordia, cell fate and tissue patterning are regulated by signals emanating from small groups of cells known as organizing centers. Intense research effort in a variety of model organisms has provided insight into how these organizing centers work. The current view is that they produce extracellular signaling molecules that belong to a relatively small number of evolutionarily conserved protein families such as the FGFs (fibroblast growth factors), TGFβs (transforming growth factors), HHs (hedgehogs) and WNTs. Cells co-ordinate their response to these signaling proteins through conserved families of transmembrane receptors, intracellular proteins and transcription factors that mediate changes in gene expression and cell behavior.

One of the goals of the Hogan Laboratory is to understand how signaling factors regulate the branching morphogenesis of the embryonic mouse lung. This organ arises from two small buds on the ventral surface of the foregut, each made up of an inner epithelial layer of endoderm, surrounded by mesenchyme. The buds undergo repetitive rounds of outgrowth and branching, giving rise to an extensive respiratory tree terminating in millions of tiny sacs - the future alveoli. We are currently focusing on the role of the FGF signaling pathway in bud outgrowth, as well novel roles for several proteins that have previously only been studied in relation to the outgrowth of nerve axons. We are also focusing on the role of the FGF, WNT and BMP signaling pathways in controlling the proliferation of multipotent progenitor cells at the tips of the lung buds and their differentiation into the progenitors of the different specialized cells of the adult lung.

Another focus of the Hogan lab is on stem cells, including the differentiation of mouse embryonic stem cells into endodermal derivatives, including the lung.