Barry T. Hinton

Education

  • BS, University of East London
  • PhD, The Babraham Institute

Primary Appointment

  • Professor, Cell Biology

Contact

Research Interest(s)

Morphogenesis of the Developing Wolffian/Epididymal duct

Research Description

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.

Selected Publications

  • Domeniconi R, Souza A, Xu B, Washington A, Hinton B. Is the Epididymis a Series of Organs Placed Side By Side? Biology of reproduction. 2016;95(1): 10. PMID: 27122633
  • Ribeiro C, Silva E, Hinton B, Avellar M. β-defensins and the epididymis: contrasting influences of prenatal, postnatal, and adult scenarios. Asian journal of andrology. 2016;18(2): 323-8. PMID: 26763543 | PMCID: PMC4770510
  • Xu B, Washington A, Domeniconi R, Ferreira Souza A, Lu X, Sutherland A, Hinton B. Protein tyrosine kinase 7 is essential for tubular morphogenesis of the Wolffian duct. Developmental biology. 2016;412(2): 219-33. PMID: 26944093 | PMCID: PMC4826835
  • Xu B, Washington A, Hinton B. Initial Segment Differentiation Begins During a Critical Window and Is Dependent upon Lumicrine Factors and SRC Proto-Oncogene (SRC) in the Mouse. Biology of reproduction. 2016;95(1): 15. PMID: 27281706
  • Murashima A, Xu B, Hinton B. Understanding normal and abnormal development of the Wolffian/epididymal duct by using transgenic mice. Asian journal of andrology. 2015;17(5): 749-55. PMID: 26112482 | PMCID: PMC4577584
  • Xu B, Washington A, Hinton B. PTEN signaling through RAF1 proto-oncogene serine/threonine kinase (RAF1)/ERK in the epididymis is essential for male fertility. Proceedings of the National Academy of Sciences of the United States of America. 2014;111(52): 18643-8. PMID: 25512490 | PMCID: PMC4284526
  • Xu B, Yang L, Hinton B. The Role of fibroblast growth factor receptor substrate 2 (FRS2) in the regulation of two activity levels of the components of the extracellular signal-regulated kinase (ERK) pathway in the mouse epididymis. Biology of reproduction. 2013;89(2): 48. PMID: 23782834 | PMCID: PMC4076368
  • Hinton B, Galdamez M, Sutherland A, Bomgardner D, Xu B, Abdel-Fattah R, Yang L. How do you get six meters of epididymis inside a human scrotum? Journal of andrology. 2011;32(6): 558-64. PMID: 21441421
  • Mital P, Hinton B, Dufour J. The blood-testis and blood-epididymis barriers are more than just their tight junctions. Biology of reproduction. 2011;84(5): 851-8. PMID: 21209417
  • Xu B, Abdel-Fattah R, Yang L, Crenshaw S, Black M, Hinton B. Testicular lumicrine factors regulate ERK, STAT, and NFKB pathways in the initial segment of the rat epididymis to prevent apoptosis. Biology of reproduction. 2011;84(6): 1282-91. PMID: 21311037 | PMCID: PMC3099589
  • Hinton B, Cooper T. The epididymis as a target for male contraceptive development. Handbook of experimental pharmacology. 2010; 117-37. PMID: 20839090
  • Snyder E, Small C, Bomgardner D, Xu B, Evanoff R, Griswold M, Hinton B. Gene expression in the efferent ducts, epididymis, and vas deferens during embryonic development of the mouse. Developmental dynamics : an official publication of the American Association of Anatomists. 2010;239(9): 2479-91. PMID: 20652947 | PMCID: PMC2939230
  • Xu B, Yang L, Lye R, Hinton B. p-MAPK1/3 and DUSP6 regulate epididymal cell proliferation and survival in a region-specific manner in mice. Biology of reproduction. 2010;83(5): 807-17. PMID: 20650883 | PMCID: PMC2959110
  • Archambeault D, Tomaszewski J, Joseph A, Hinton B, Yao H. Epithelial-mesenchymal crosstalk in Wolffian duct and fetal testis cord development. Genesis (New York, N.Y. : 2000). 2008;47(1): 40-8. PMID: 18979542 | PMCID: PMC2877590
  • Cotton L, O'Bryan M, Hinton B. Cellular signaling by fibroblast growth factors (FGFs) and their receptors (FGFRs) in male reproduction. Endocrine reviews. 2008;29(2): 193-216. PMID: 18216218 | PMCID: PMC2528845
  • Joseph A, Yao H, Hinton B. Development and morphogenesis of the Wolffian/epididymal duct, more twists and turns. Developmental biology. 2008;325(1): 6-14. PMID: 18992735 | PMCID: PMC2639655
  • Yang L, Fox S, Kirby J, Troan B, Hinton B. Putative regulation of expression of members of the Ets variant 4 transcription factor family and their downstream targets in the rat epididymis. Biology of reproduction. 2006;74(4): 714-20. PMID: 16394217
  • Kirby J, Yang L, Labus J, Lye R, Hsia N, Day R, Cornwall G, Hinton B. Characterization of epididymal epithelial cell-specific gene promoters by in vivo electroporation. Biology of reproduction. 2004;71(2): 613-9. PMID: 15115732