Journal article

Mis-expression of grainyhead-like transcription factors in zebrafish leads to defects in enveloping layer (EVL) integrity, cellular morphogenesis and axial extension

Lee B Miles, Charbel Darido, Jan Kaslin, Joan K Heath, Stephen M Jane, Sebastian Dworkin

SCIENTIFIC REPORTS | NATURE PUBLISHING GROUP | Published : 2017

Abstract

The grainyhead-like (grhl) transcription factors play crucial roles in craniofacial development, epithelial morphogenesis, neural tube closure, and dorso-ventral patterning. By utilising the zebrafish to differentially regulate expression of family members grhl2b and grhl3, we show that both genes regulate epithelial migration, particularly convergence-extension (CE) type movements, during embryogenesis. Genetic deletion of grhl3 via CRISPR/Cas9 results in failure to complete epiboly and pre-gastrulation embryonic rupture, whereas morpholino (MO)-mediated knockdown of grhl3 signalling leads to aberrant neural tube morphogenesis at the midbrain-hindbrain boundary (MHB), a phenotype likely due..

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Grants

Awarded by Australian National Health and Medical Research Council (NHMRC)


Awarded by Australian Research Council (ARC) Discovery Early Career Researcher Awards (DECRA)


Awarded by VCA Clare Oliver Memorial


Awarded by Association for International Cancer Research (AICR)


Funding Acknowledgements

The authors wish to thank Dr. Peter Lock at the La Trobe Institute for Molecular Science (LIMS) Bioimaging facility for his technical expertise. The authors were supported by grants from the Australian National Health and Medical Research Council (NHMRC, APP1063837 and APP1106697) the Australian Research Council (ARC) Discovery Early Career Researcher Awards (DECRA, DE140100500), and the La Trobe University Research Focus Area of Securing Food, Water and the Environment. CD is a Victorian Cancer Agency (VCA) Mid-Career Fellow (CR_16/5985) and was supported by a fellowship from the VCA Clare Oliver Memorial (COF11_04) and by a grant (11-0060) from The Association for International Cancer Research (AICR).