Development of the External Genitalia and Hypospadias

In humans and mice, mutations in Hoxa13 cause hypospadias, a common birth defect affecting the growth and closure of the external genitalia.  In humans, hypospadias affects 1 in 125 live male births each year making this malformation one of the most prevalent defects in industrialized nations including the United States.  

development of external genitalia

Stadler   Nature Reviews Genetics  4:1-5  2003.

To dissect the transcriptional hierarchy regulated by HOXA13 in the external genitalia the Stadler Laboratory uses Affymetrix microarrays, RNAseq, and ChIP-seq to define the target genes regulated by HOXA13 that are necessary for the normal development of the external genitalia.  To interpret the ChIP and Affymetrix results in the context of the Hoxa13 mutant phenotype we have identified the HOXA13 binding site and have applied it to the A13-ChIP and Affymetrix data to define the target genes directly regulated by HOXA13 in the external genitalia (Knosp et al., 2007, Shaut et al., 2008).  The identification of the HOXA13 binding site places us in a unique position to accurately identify the HOXA13 transcriptome in the external genitalia and allows us to investigate the developmental basis for hypospadias with strong scientific rigor.