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Hedgehog–FGF signaling axis patterns anterior mesoderm during gastrulation

Journal Article · · Proceedings of the National Academy of Sciences of the United States of America
 [1];  [1];  [1];  [2];  [1];  [1];  [1];  [3];  [1];  [3];  [3];  [2];  [4];  [5];  [6];  [1]
  1. Department of Pediatrics, University of Chicago, Chicago, IL 60637,, Department of Pathology, University of Chicago, Chicago, IL 60637,, Department of Human Genetics, University of Chicago, Chicago, IL 60637,
  2. Department of Molecular and Functional Genomics, Geisinger Clinic, Weis Center for Research, Danville, PA 17822,, Department of Pediatrics, University of Utah, Salt Lake City, UT 84112,, Department of Human Genetics, University of Utah, Salt Lake City, UT 84112,
  3. Department of Medicine, University of Chicago, Chicago, IL 60637,
  4. Department of Medicine, University of Chicago, Chicago, IL 60637,, Center for Nanoscale Materials, Argonne National Laboratory, Lemont, IL 60439,
  5. Department of Cell Biology and Physiology, University of North Carolina, Chapel Hill, NC 27599
  6. Department of Human Genetics, University of Chicago, Chicago, IL 60637,
Significance

Anterior–posterior axis patterning is a fascinating but poorly understood developmental process. Single-cell sequencing was utilized to interrogate patterning abnormalities in a mesoderm-specific Hedgehog (Hh) pathway mutant, which revealed selective anterior mesoderm defects. We found that Hh signaling was required for fibroblast growth factor (FGF) pathway activity in nascent mesoderm during gastrulation. Mouse genetics, cell biology, and genomic experiments indicate that FGF signaling acts downstream of Hh signaling in nascent mesoderm for anterior mesoderm morphogenesis. This work demonstrates the utility of applying single-cell technologies to resolve complex developmental phenotypes. Here, it revealed a role for Hh signaling from the node in organizing anterior mesoderm morphogenesis, independent of its role in left–right determination, by promoting FGF signaling in gastrulating mesoderm.

Sponsoring Organization:
USDOE
Grant/Contract Number:
AC02-06CH11357
OSTI ID:
1633943
Journal Information:
Proceedings of the National Academy of Sciences of the United States of America, Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Issue: 27 Vol. 117; ISSN 0027-8424
Publisher:
Proceedings of the National Academy of SciencesCopyright Statement
Country of Publication:
United States
Language:
English

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