Oral Presentation ESA-SRB Conference 2015

Dynamin 2: an essential regulator of male germ cell development (#11)

Kate A Redgrove 1 , Ilana R McKeough 1 , Victoria Pye 1 , Janet E Holt 1 , Brett Nixon 1 , Adam McCluskey 1 , Eileen A McLaughlin 1
  1. University of Newcastle, CALLAGHAN, NSW, Australia

The dynamin (Dnm) family are a group of GTPases best known for their roles in membrane fission and fusion events such as endocytosis, as well as in the regulation of cytoskeletal components. A role for Dnm 1/2 has recently been identified during the acrosome reaction in spermatozoa, however little is known about Dnm function in the early male germline. We examined the expression profiles of the three mammalian Dnm genes (Dnm 1,2 and 3) in the mouse testes and isolated male germ cell/spermatozoa, and identified Dnm1 and 2 as the only family members expressed at detectable levels in germ cells. To examine consequences of Dnm2 loss in the male germ line, we created an male germ cell-specific Dnm2 mouse knockout, (DDX4Cre;Dnm2 lox/lox). Dnm2 knockout animals failed to form mature spermatozoa with complete spermatogenic arrest at the zygotene stage of meiotic development. Analysis revealed significant apoptosis in cells at post natal D15 and a complete absence of pachytene spermatocytes in all null animals.To further examine Dnm2 function in in the male germ line, we  characterized the phosphorylating kinase and phosphatase to establish the molecular switch mechanisms in the meiotic and post-meiotic cells.  Our studies indicate that Dnm2 is essential for male germ cell development during the early phases of spermatogenesis, and that other Dnm family members are unable to compensate in its absence. We also identified a unique role for Dnm2 in regulating meiosis, which highlights key features of the role of Dnm2 in chromosome dynamics.