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ZFIN ID: ZDB-PUB-180629-6
Pitx2c orchestrates embryonic axis extension via mesendodermal cell migration
Collins, M.M., Maischein, H.M., Dufourcq, P., Charpentier, M., Blader, P., Stainier, D.Y.
Date: 2018
Source: eLIFE   7: (Journal)
Registered Authors: Blader, Patrick, Dufourcq, Pascale, Maischein, Hans-Martin, Stainier, Didier
Keywords: Pitx2c, cell migration, chemokine signaling, developmental biology, gastrulation, integrin-fibronectin interaction, zebrafish
Microarrays: GEO:GSE114671
MeSH Terms:
  • Animals
  • Animals, Genetically Modified
  • Body Patterning/genetics
  • Cell Movement/genetics*
  • Cell Shape
  • Chemokines/genetics
  • Chemokines/metabolism
  • Embryo, Nonmammalian
  • Embryonic Development/genetics*
  • Endoderm/cytology
  • Endoderm/metabolism
  • Epithelial Cells/cytology
  • Epithelial Cells/metabolism*
  • Extracellular Matrix Proteins/genetics
  • Extracellular Matrix Proteins/metabolism
  • Gastrulation/genetics
  • Gene Expression Regulation, Developmental*
  • Integrins/genetics
  • Integrins/metabolism
  • Mutation
  • Notochord/cytology
  • Notochord/metabolism
  • Time-Lapse Imaging
  • Transcription Factors/genetics*
  • Transcription Factors/metabolism
  • Transcriptome
  • Zebrafish/genetics*
  • Zebrafish/growth & development
  • Zebrafish/metabolism
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
  • Zygote/cytology
  • Zygote/growth & development
  • Zygote/metabolism
PubMed: 29952749 Full text @ Elife
Pitx2c, a homeodomain transcription factor, is classically known for its left-right patterning role. However, an early wave of pitx2 expression occurs at the onset of gastrulation in several species, indicating a possible earlier role that remains relatively unexplored. Here we show that in zebrafish, maternal-zygotic (MZ) pitx2c mutants exhibit a shortened body axis indicative of convergence and extension (CE) defects. Live imaging reveals that MZpitx2c mutants display less persistent mesendodermal migration during late stages of gastrulation. Transplant data indicate that Pitx2c functions cell non-autonomously to regulate this cell behavior by modulating cell shape and protrusive activity. Using transcriptomic analyses and candidate gene approaches, we identify transcriptional changes in components of the chemokine-ECM-integrin dependent mesendodermal migration network. Together, our results define pathways downstream of Pitx2c that are required during early embryogenesis and reveal novel functions for Pitx2c as a regulator of morphogenesis.