Sean Li (PI)
Harvard Medical School
Congenital penile anomalies including hypospadias and ambiguous genitalia occur in 7.8/1,000 newborns. Despite their biological and medical significance, the molecular basis of such birth defects remains largely unexplained. Moreover, the critical GT-specific downstream effectors of sex hormones are yet to be defined. Our findings suggest that the vGTMspecific dimorphic genes may play critical roles in the gender-specific GT differentiation. We hypothesize that Wnt4 expressed from the GT epithelium functions as the permissive signal and; inductive signals including the sex hormones reprogram the GT-specific dimorphic enhancers and induce dimorphic gene expression to form the penis in males and clitoris in female. We aim to determine whether Wnt4 expressed from the GT epithelium is the permissive signal required for penile development, whether sex hormones reprogram the GT-specific landscape of transcription enhancers to control dimorphic gene expression and identify critical GT-specific downstream effectors of sex hormones that induce dimorphic GT differentiation.