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Pkd1l1 establishes left-right asymmetry and physically interacts with Pkd2
Sarah Field1, Kerry-Lyn Riley, Daniel T Grimes
1Mammalian Genetics Unit, MRC Harwell, Harwell Science and Innovation Campus, Oxfordshire OX11 0RD, UK.
Development (Cambridge, England)
|February 11, 2011
Summary
Pkd1l1 is identified as a key protein in mammalian left-right body patterning. It interacts with Pkd2, supporting the two-cilia hypothesis for embryonic development.
Area of Science:
- Developmental biology
- Genetics
- Cell biology
Background:
- Left-right (L-R) asymmetry in mammals is critical for organ positioning.
- This asymmetry is established by cilia-driven nodal flow and subsequent gene expression.
- The sensory mechanism for flow detection, particularly the partner for Pkd2, remained unknown.
Purpose of the Study:
- To identify the putative sensory partner of Pkd2 involved in L-R patterning.
- To elucidate the role of Pkd1l1 in mammalian embryonic L-R asymmetry.
- To validate the two-cilia hypothesis in L-R axis determination.
Main Methods:
- Genetic analysis of Pkd1l1 and Pkd2 point mutants in mice.
- Morphological and molecular assessment of embryonic development and gene expression.
- Cilia motility and localization studies.
- Biochemical co-immunoprecipitation assays to test protein interactions.
Main Results:
- Pkd1l1 mutants phenocopied Pkd2 mutants, showing defects in asymmetric gene expression and lung isomerism.
- Pkd1l1 and Pkd2 were found to localize to cilia and physically interact.
- Cilia morphology and motility were unaffected in mutants, indicating downstream function of nodal flow.
Conclusions:
- Pkd1l1 is identified as the missing Pkd2 binding partner essential for L-R patterning.
- These findings provide strong support for the two-cilia hypothesis in establishing embryonic sidedness.
- Pkd1l1 and Pkd2 function downstream of nodal flow in the embryonic node.
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