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Developmental roles for Srf, cortical cytoskeleton and cell shape in epidermal spindle orientation
Chen Luxenburg1, H Amalia Pasolli, Scott E Williams
1Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, New York 10065, USA.
Nature Cell Biology
|February 22, 2011
Summary
Serum response factor (SRF) is crucial for skin development. Its loss disrupts cell shape, division, and skin barrier formation by affecting actin dynamics and cell rigidity.
Area of Science:
- Developmental Biology
- Cell Biology
- Dermatology
Background:
- Epidermal development involves stratification and differentiation to form the skin barrier.
- Mechanisms governing epidermal embryogenesis, including actin dynamics, spindle reorientation, and Notch signaling, are not fully understood.
Purpose of the Study:
- To investigate the role of serum response factor (SRF) in epidermal differentiation and embryogenesis.
- To elucidate the underlying mechanisms of SRF-dependent epidermal development.
Main Methods:
- Conditional targeting of the transcription factor SRF in epidermal development.
- Analysis of cellular morphology, actin dynamics, and mitotic events in SRF-ablated cells.
- In vivo and in vitro experiments using actin inhibitors and shRNA knockdown.
Main Results:
- SRF ablation led to downregulation of actins and their regulators.
- SRF-deficient cells showed a diminished cortical actin network and failed to round up during mitosis.
- Altered phosphorylation of ERM proteins and cortical myosin-IIA was observed, impacting actomyosin network rigidity and cell shape.
Conclusions:
- SRF is essential for maintaining cortical actin integrity and proper cell shape during epidermal development.
- SRF loss disrupts spindle orientation, asymmetric cell division, stratification, and differentiation, leading to skin barrier defects.
- These findings link SRF to the regulation of cellular mechanics critical for skin development.
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