Proceedings of the National Academy of Sciences - PNAS, 2020-07, Vol.117 (27), p.15712-15723
2020
Volltextzugriff (PDF)
Details
- Autor(en) / Beteiligte
- Titel
- Hedgehog–FGF signaling axis patterns anterior mesoderm during gastrulation
- Ist Teil von
- Proceedings of the National Academy of Sciences - PNAS, 2020-07, Vol.117 (27), p.15712-15723
- Ort / Verlag
- United States: National Academy of Sciences
- Erscheinungsjahr
- 2020
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- The mechanisms used by embryos to pattern tissues across their axes has fascinated developmental biologists since the founding of embryology. Here, using single-cell technology, we interrogate complex patterning defects and define a Hedgehog (Hh)–fibroblast growth factor (FGF) signaling axis required for anterior mesoderm lineage development during gastrulation. Single-cell transcriptome analysis of Hh-deficient mesoderm revealed selective deficits in anterior mesoderm populations, culminating in defects to anterior embryonic structures, including the pharyngeal arches, heart, and anterior somites. Transcriptional profiling of Hh-deficient mesoderm during gastrulation revealed disruptions to both transcriptional patterning of the mesoderm and FGF signaling for mesoderm migration. Mesoderm-specific Fgf4/Fgf8 double-mutants recapitulated anterior mesoderm defects and Hh-dependent GLI transcription factors modulated enhancers at FGF gene loci. Cellular migration defects during gastrulation induced by Hh pathway antagonism were mitigated by the addition of FGF4 protein. These findings implicate a multicomponent signaling hierarchy activated by Hh ligands from the embryonic node and executed by FGF signals in nascent mesoderm to control anterior mesoderm patterning.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0027-8424eISSN: 1091-6490DOI: 10.1073/pnas.1914167117Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7354932
- Format
- –
- Schlagworte
- Animals, Biological Sciences, Body Patterning - genetics, Cell Lineage - genetics, Chick Embryo, Defects, Embryology, Embryos, Enhancers, Fibroblast growth factor 4, Fibroblast Growth Factor 4 - genetics, Fibroblast growth factor 8, Fibroblast Growth Factor 8 - genetics, Fibroblast Growth Factors - genetics, Gastrula - growth & development, Gastrula - metabolism, Gastrulation, Gastrulation - genetics, Gene expression, Gene Expression Regulation, Developmental - genetics, Growth factors, Hedgehog protein, Hedgehog Proteins - genetics, Kinases, Mesoderm, Mesoderm - growth & development, Mesoderm - metabolism, Mice, Pattern formation, Patterning, Pharynx, Signal Transduction - genetics, Signaling, Single-Cell Analysis, Somites, Transcription factors, Transcriptome - genetics, Zinc Finger Protein GLI1 - genetics