The role of grainyhead-like 3 (grhl3) in the regulation of gastrulation, axial formation and early skin development

LB Miles1, J Tang1, J Kaslin1, SM Jane1, JK Heath2 and S Dworkin1,3

  1. Monash University, Clayton Campus, Melbourne, VIC, 3800
  2. Walter and Eliza Hall Institute, 1G Royal Pde, Parkville, VIC, 3050
  3. La Trobe University, Bundoora, VIC, 3086

The highly conserved transcription factor grainyhead-like 3 (grhl3) is a critical regulator of embryogenesis, involved in formation of the neural tube, closure of the secondary palate, development of the epidermal barrier, and playing an important role in wound healing. We are investigating the role for the grhl3 transcription factor during development, using the highly-tractable zebrafish as our model. Our preliminary data show that grhl3 is strongly and specifically activated at the maternal-zygotic transition (MZT) preceding gastrulation, and subsequently that grhl3 is required for EVL/periderm formation and maintenance. Our preliminary results indicate that both loss and overexpression of grhl3 leads to severe problems during gastrulation, resulting in reduced epiboly, a split trunk/axis, reduction in body size, defects in EVL cell formation, and craniofacial malformations. We are currently generating null mutant grhl3 zebrafish (using CRSIPR/Cas9 genome modification) to extend our preliminary findings, as well as a transgenic line capable of inducible grhl3 overexpression after heat shock treatment. Using advanced molecular and bioinformatics approaches, our current focus is on identifying novel grhl3 target genes, protein binding partners, and downstream signalling pathways which operate during early embryonic development.