Hinton, Barry T.
Professor, Cell Biology
- BS, Biochemistry and Pharmacology, University of East London
- PhD, Reproductive Biology, The Babraham Institute
Cell and Developmental Biology, Development, Stem Cells & Regeneration
Morphogenesis of the Developing Wolffian/Epididymal duct
Wolffian/Epididymal duct Morphogenesis.
The formation of tubes is a fundamental biological process during the genesis of many organs, for example, kidney, intestine, brain, heart, and lungs. In fact, very few organs do not form tubular structures at some point in their development. Formation of the tubular structure is then followed by unique morphogenic events in each organ to generate their final adult structure. The morphogenesis of the Wolffian/epididymal duct is unusual in that it exhibits a unique pattern in that it forms a simple tube and then systematically elongates and coils dramatically. Surprisingly, the fully developed epididymis is 1.2 meters long in the mouse, 3 meters long in the rat and a remarkable 6 meters long in the human. The goal of this laboratory is to understand the mechanisms by which this important biological tube elongates and coils because without a fully developed and functional epididymis, male infertility will result. We are especially interested in the contribution of cell proliferation and cell rearrangements towards duct elongation. Data obtained from using mice that are null for protein tyrosine kinase 7 supports the hypothesis that cell rearrangements are under the regulation of the planar cell polarity/non-canonical Wnt pathway.
We are also examining the regulation of cell proliferation and cell differentiation in the initial segment, the most proximal region of the epididymis. The failure of this region to develop properly results in male infertility. Interestingly, the epididymis rarely succumbs to cancer, and it is not clear how this is achieved. Testicular luminal fluid growth factors, e.g. FGFs, maintain high activities of the components of the MAPK pathway, especially pMAPK1/3, during postnatal development, which in turn maintains cell proliferation during this developmental period. Using a conditional knockout approach, we have examined the role of the tumor suppressor, Phosphatase and Tensin Homolog (PTEN) in the initial segment. We have discovered that PTEN is crucial for the development of cell differentiation and therefore, male fertility. Loss of PTEN did not result in cancer of the epididymis.