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Huntingtin regulates mammary stem cell division and differentiation
Salah Elias1, Morgane S Thion1, Hua Yu1
1Institut Curie, Orsay 91405, France ; CNRS UMR 3306, Orsay 91405, France ; INSERM U1005, Orsay 91405, France.
Stem Cell Reports
|April 22, 2014
Summary
Huntingtin protein is crucial for mammary stem cell division orientation during development. Its depletion disrupts mammary gland morphogenesis by misorienting mitotic spindles, impacting progenitor cells.
Area of Science:
- Cell Biology
- Developmental Biology
- Genetics
Background:
- Mechanisms of mitotic spindle orientation in mammary gland development are poorly understood.
- Huntingtin protein, implicated in Huntington's disease, is present in mammary gland cells during development.
Purpose of the Study:
- To investigate the role of huntingtin in mammary gland morphogenesis and mitotic spindle orientation.
- To elucidate the molecular mechanisms by which huntingtin regulates spindle orientation.
Main Methods:
- Utilized Keratin 5-driven depletion of huntingtin in mouse models.
- Performed cell culture experiments to analyze mitotic spindle orientation.
- Investigated protein interactions and localization using techniques like immunofluorescence and co-immunoprecipitation.
Main Results:
- Huntingtin depletion decreased progenitor cell pools and altered mammary gland development.
- Mitotic spindle misorientation was observed in huntingtin-depleted basal progenitors.
- Huntingtin regulates spindle orientation via dynein-dependent mechanisms, interacting with NUMA and LGN.
- Huntingtin is essential for the cortical localization of key spindle orientation proteins.
Conclusions:
- Huntingtin is a key component in the pathway regulating mammary stem cell division orientation.
- This regulation has potential implications for mammary stem cell self-renewal and differentiation.
- Findings suggest a novel role for huntingtin beyond its known association with neurodegenerative disease.
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