Homeodomain Proteins in Epithelial Differentiation
Dr. Liang Ma's laboratory is interested in studying how Msx homeobox genes control hair differentiation and hair cycling. Mice deficient for Msx2 exhibit cyclic alopecia providing a unique model to study the molecular mechanism of hair loss. Many signaling pathways are active during hair differentiation and hair cycling. Integrating Msx genes into the existing pathway constitutes a major focus of the laboratory. We have shown in the hair cortex, Msx2 functions in a genetic pathway upstream to Foxn1 and cortex keratins. Both Msx2 and Foxn1 are required for Notch signal pathway in the hair follicle. Currently we are trying to identify direct Msx2 targets in the hair follicle, which may shed light on the molecular mechanism of alopecia.
In addition to our interest in hair biology, the lab is also interested in transcription factors regulating uterine epithelial differentiation. One approach to uncover genes that are important for uterine development is to identify genes whose expression is altered en route to abnormal uterine differentiation. Proper uterine cytodifferentiation can be disturbed by developmental exposure to a synthetic estrogen diethylstilbestrol (DES). DES was the first synthetic estrogenic compound orally administered to pregnant women (from 1947 to 1971) in an effort to preserve pregnancy, and was later found to be a teratogen for the developing reproductive tracts. Using a combination of microarray technology and in situ hybridization, we have identified an array of transcription factors whose interesting expression profiles suggest an important role in regulating uterine cytodifferentiation. Currently we are using transgenic and knockout technologies to test their in vivo function.