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Fgf signalling triggers an intrinsic mesodermal timer that determines the duration of limb patterning
Sofia Sedas Perez1, Caitlin McQueen1,2, Holly Stainton1
1School of Biosciences, University of Sheffield, Western Bank, Sheffield, S10 2TN, UK.
Nature Communications
|September 20, 2023
Summary
Fibroblast growth factors (FGFs) transiently trigger limb development patterning. FGF signalling is not required for maintaining limb patterning, which is controlled by the mesodermal transcriptome.
Area of Science:
- Developmental biology
- Molecular biology
- Genetics
Background:
- Limb patterning along the proximo-distal axis is controlled by complex signalling between the apical ectodermal ridge (AER) and mesoderm.
- The essential in vivo requirement for AER-Fibroblast Growth Factor (FGF) signalling complicates understanding its precise roles.
Purpose of the Study:
- To elucidate the exact roles of AER-FGF signalling in limb patterning.
- To investigate the maintenance of limb patterning independent of FGF signalling.
Main Methods:
- Development of an ex vivo chick wing tissue explant system that replicates in vivo parameters.
- Inhibition experiments and RNA-sequencing to analyze gene expression and signalling pathways.
Main Results:
- FGF signalling plays a transient role in triggering the distal patterning phase of limb development.
- FGFs are dispensable for maintaining the mesodermal transcriptome, which governs proliferation, differentiation timing, and patterning duration.
- FGF signalling also maintains AER-related gene expression and suppresses myogenesis.
Conclusions:
- A simple logic for limb patterning duration was identified, potentially applicable to other developmental systems.
- The mesodermal transcriptome intrinsically controls key aspects of limb patterning timing and progression.
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