( ed that reducing expression of E-cadher...)Hirsute Or Hairless? Two Proteins May Spell The Difference

ed that reducing expression of E-cadherin—a membrane protein that forms the adhesive junctions between epidermal cells—is essential for allowing the cell remodeling required for bud formation. Here, the authors analyze the timing of external signals against the response of targeted cells to determine how targeted cells translate signals into changes in cell adhesion and remodeling, proliferation, and differentiation—the agents of most types of organogenesis.

Since Snail, a protein that impedes the transcription of a subset of genes, functions in many developmental processes requiring epithelial remodeling, the authors reasoned it might do the same in hair bud formation. Working with developing mouse embryos, they saw a spike in Snail expression on embryonic day 17.5, coinciding with hair bud formation, enhanced cell proliferation, and the down-regulation of E-cadherin. Artificially sustaining Snail expression in the skin of transgenic mice caused abnormal levels of cell proliferation in the epidermis and reduced cell adhesion.

Working with skin keratinocytes, precursors of hair fibers, Fuchs and colleagues explored several signaling proteins known to be involved in bud formation as possible activators of Snail expression. When the authors treated keratinocytes with small amounts of one stimulator, TGF-β2, they saw “rapid and transient induction of Snail.?Snail proteins were absent from 17.5-day-old knockout mice lacking TGF-β2 but not from their nonmutant littermates. Conversely, transgenic mice with elevated TGF-β2 signaling activity displayed ectopic expression of Snail. Knockout mice lacking TGF-β2 also showed higher levels of E-cadherin—normally down-regulated by Snail—than their nonmutant littermates.

Altogether, these findings suggest that TGF-β2 signaling transiently induces Snail, which in turn down-regulates E-cadherin and activates a proliferation pathway in the developing bud. Reduced E-cadherin, the authors conclude, appears to co
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Source:PLoS

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