PUBLICATION

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

Authors
Miles, L.B., Darido, C., Kaslin, J., Heath, J.K., Jane, S.M., Dworkin, S.
ID
ZDB-PUB-171216-5
Date
2017
Source
Scientific Reports   7: 17607 (Journal)
Registered Authors
Dworkin, Seb, Heath, Joan K., Jane, Stephen M.
Keywords
none
MeSH Terms
  • Animals
  • Body Patterning/genetics
  • Cell Movement
  • DNA-Binding Proteins/genetics
  • Embryo, Mammalian/metabolism
  • Embryonic Development/physiology
  • Gene Expression Regulation, Developmental/genetics
  • Mesencephalon/metabolism
  • Morphogenesis
  • Morpholinos/metabolism
  • Neural Tube/metabolism
  • Phenotype
  • Rhombencephalon/metabolism
  • Signal Transduction
  • Transcription Factors/metabolism
  • Transcription Factors/physiology*
  • Zebrafish/genetics
  • Zebrafish/metabolism
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
  • Zebrafish Proteins/physiology*
PubMed
29242584 Full text @ Sci. Rep.
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 to a compromised overlying enveloping layer (EVL). Further disruptions of grhl3-dependent pathways (through co-knockdown of grhl3 with target genes spec1 and arhgef19) confirm significant MHB morphogenesis and neural tube closure defects. Concomitant MO-mediated disruption of both grhl2b and grhl3 results in further extensive CE-like defects in body patterning, notochord and somite morphogenesis. Interestingly, over-expression of either grhl2b or grhl3 also leads to numerous phenotypes consistent with disrupted cellular migration during gastrulation, including embryo dorsalisation, axial duplication and impaired neural tube migration leading to cyclopia. Taken together, our study ascribes novel roles to the Grhl family in the context of embryonic development and morphogenesis.
Genes / Markers
Figures
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Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes