Chad Vezina Group (GUDMAP1)
Project Description
It is believed that some of the growth mechanisms activated normally during prostate development are reactivated inappropriately during prostate disease. The developing fetal mouse prostate provides an excellent model for elucidating these prostate growth mechanisms. Prostate ductal development is initiated in the fetal male by androgen-dependent growth of epithelial prostatic buds into surrounding urogenital sinus (UGS) mesenchyme. Collaboration between androgen receptors and other less understood signals specifies location, number, and timing of prostatic budding, and later in development facilitates prostate ductal branching morphogenesis and cellular differentiation. The goal of this project is to establish a temporal and spatial atlas of gene expression during key stages of fetal and neonatal mouse prostate development.
Approach
We will use in situ hybridization to assess expression patterns of select mRNAs in fetal male mouse UGS sections at daily intervals from 14 days post coitum (dpc) to birth, which spans the embryonic period when circulating male hormones pattern and initiate prostate development. Additionally, female UGS sections will be assessed daily from 15-17 dpc and will be compared with male sections to identify sexually dimorphic gene expression patterns that associate temporally with prostatic bud initiation in males. Expression of mRNAs will also be visualized 5 days after birth, during prostate branching morphogenesis, and 50 days after birth, shortly after puberty.
Relationship to the overall goals of GUDMAP
Identification of mRNA markers of each of the mouse prostate cell types is necessary for the long-term GUDMAP goal of comparative gene expression profiling among prostate cell types and will be useful for marking and mapping the fate of prostate cell populations during development, differentiation, senescence, and disease. Additionally, our results will identify previously unrecognized signaling pathways that contribute to androgen-dependent prostate growth and development.
