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Culture of Murine Embryonic Metatarsals: A Physiological Model of Endochondral Ossification
Published on: December 3, 2016
Intraflagellar transport is essential for endochondral bone formation
Courtney J Haycraft1, Qihong Zhang, Buer Song
1Department of Cell Biology, University of Alabama at Birmingham, Birmingham, AL 35294-0005, USA.
Development (Cambridge, England)
|December 15, 2006
Summary
Intraflagellar transport (IFT) is essential for cilia formation and limb development. Disrupting IFT in limb mesenchyme causes polydactyly and abnormal skeletal patterning by affecting key signaling pathways.
Area of Science:
- Developmental Biology
- Cell Biology
- Genetics
Background:
- Cilia are increasingly recognized for their critical roles in mammalian development.
- Intraflagellar transport (IFT) is crucial for cilia assembly, and its disruption leads to severe developmental defects and early lethality.
- Studying cilia's role in later developmental stages, like limb development, has been challenging due to early lethality in IFT mutants.
Purpose of the Study:
- To investigate the specific role of cilia in mammalian limb development.
- To determine how disrupting intraflagellar transport (IFT) in limb mesenchymal cells affects skeletal patterning and outgrowth.
Main Methods:
- Generated a conditional allele of the IFT protein Ift88 (polaris) using the Cre-lox system.
- Disrupted cilia formation in specific cell populations within the developing limb, particularly in mesenchymal cells.
- Analyzed limb development, digit patterning, and associated signaling pathways (Shh, Ihh).
Main Results:
- Cilia disruption in limb mesenchyme, but not ectoderm, caused extensive polydactyly and abnormal anteroposterior digit patterning.
- Limb outgrowth was reduced, linked to disrupted Indian hedgehog (Ihh) signaling during endochondral bone formation.
- Abnormal Shh pathway activity was observed, and ectopic chondrocyte-like cells appeared in mutant limbs.
Conclusions:
- Intraflagellar transport (IFT) is essential for normal appendicular skeleton formation.
- Cilia in limb mesenchyme regulate multiple signaling pathways, including Shh and Ihh, critical for limb patterning and skeletal development.
- Conditional disruption of cilia provides insights into their role in later developmental processes previously obscured by early lethality.
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