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A High-throughput Cell Microarray Platform for Correlative Analysis of Cell Differentiation and Traction Forces
Published on: March 1, 2017
Asymmetric cell divisions promote Notch-dependent epidermal differentiation
Scott E Williams1, Slobodan Beronja, H Amalia Pasolli
1Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, New York 10065, USA.
Nature
|February 19, 2011
Summary
Stem cell divisions control tissue development. This study reveals how regulating spindle orientation in mouse skin progenitor cells is crucial for proper skin stratification and barrier formation.
Area of Science:
- Developmental biology
- Cell biology
- Tissue engineering
Background:
- Stem and progenitor cells divide asymmetrically to balance proliferation and differentiation.
- Invertebrate studies identified protein complexes regulating cell polarity and spindle positioning during mitosis.
Purpose of the Study:
- Investigate the role of spindle orientation in regulating asymmetric cell divisions during mouse skin development.
- Determine the involvement of LGN, NuMA, and dynactin in this process.
- Understand the downstream effects of compromised asymmetric divisions on skin architecture.
Main Methods:
- Utilized in vivo skin-specific lentiviral RNA interference in mouse models.
- Assessed defects in stratification, differentiation, and barrier formation.
- Investigated the role of Notch signaling as a downstream effector.
Main Results:
- Provided direct evidence for the involvement of LGN (Gpsm2), NuMA, and dynactin (Dctn1) in regulating spindle orientation in mouse skin progenitors.
- Demonstrated that compromising asymmetric cell divisions leads to severe defects in skin stratification, differentiation, and barrier function.
- Implicated Notch signaling as a key pathway affected by these defects.
Conclusions:
- Spindle orientation is critical for establishing proper tissue architecture during mammalian skin development.
- LGN, NuMA, and dynactin are key regulators of asymmetric cell division in skin progenitors.
- RNA interference in vivo is an effective tool for studying complex genetic interactions in mammalian development.
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