Pitx2c orchestrates embryonic axis extension via mesendodermal cell migration

Pitx2c, a homeodomain transcription factor, is classically known for its left-right patterning role. However, an early wave of 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, mat...

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Bibliographic Details
Published in:eLife 2018-06, Vol.7
Main Authors: Collins, Michelle M, Maischein, Hans-Martin, Dufourcq, Pascale, Charpentier, Marine, Blader, Patrick, Stainier, Didier Yr
Format: Article
Language:English
Subjects:
Animals
Animals, Genetically Modified
Body Patterning - genetics
Cell migration
Cell Movement - genetics
Cell Shape
Cell size
chemokine signaling
Chemokines - genetics
Chemokines - metabolism
Datasets
Defects
Developmental Biology
Embryo, Nonmammalian
Embryogenesis
Embryonic Development - genetics
Endoderm - cytology
Endoderm - metabolism
Epithelial Cells - cytology
Epithelial Cells - metabolism
Experiments
Extracellular matrix
Extracellular Matrix Proteins - genetics
Extracellular Matrix Proteins - metabolism
Gastrulation
Gastrulation - genetics
Gene Expression Regulation, Developmental
Genes
Homeobox
integrin-fibronectin interaction
Integrins - genetics
Integrins - metabolism
Morphogenesis
Mutation
Notochord - cytology
Notochord - metabolism
Pitx2c
Software
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
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Summary:Pitx2c, a homeodomain transcription factor, is classically known for its left-right patterning role. However, an early wave of 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) mutants exhibit a shortened body axis indicative of convergence and extension (CE) defects. Live imaging reveals that MZ 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.
ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.34880