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Asymmetric cell divisions promote Notch-dependent epidermal differentiation
Open accessAbstract
Stem and progenitor cells use asymmetric cell divisions to balance proliferation and differentiation. Evidence from invertebrates shows that this process is regulated by proteins asymmetrically distributed at the cell cortex during mitosis: Par3-Par6-aPKC, which confer polarity, and Gα(i)-LGN/AGS3-NuMA-dynein/dynactin, which govern spindle positioning. Here we focus on developing mouse skin, where progenitor cells execute a switch from symmetric to predominantly asymmetric divisions concomitant with stratification. Using in vivo skin-specific lentiviral RNA interference, we investigate spindle orientation regulation and provide direct evidence that LGN (also called Gpsm2), NuMA and dynactin (Dctn1) are involved. In compromising asymmetric cell divisions, we uncover profound defects in stratification, differentiation and barrier formation, and implicate Notch signalling as an important effector. Our study demonstrates the efficacy of applying RNA interference in vivo to mammalian systems, and the ease of uncovering complex genetic interactions, here to gain insights into how changes in spindle orientation are coupled to establishing proper tissue architecture during skin development.
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“Notch signalling promotes differentiation of stem cell progeny in the interfollicular epidermis and hair follicles82,83.”
From Molecular regulation of stem cell quiescence (2013) · cites this paper as [83]
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Metadata
- Authors
- Williams, S. E., Beronja, S., Pasolli, H. A., & Fuchs, E.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Fuchs, Elaine
- Venue
- Nature
- Published
- 2011-02
- Volume
- 470
- Issue
- 7334
- Pages
- 353-358
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3077085
- OpenAlex
- W2038970717
- Cited by
- 406
- References
- 51
- Citations by year
- 2026: 9 · 2025: 13 · 2024: 8 · 2023: 13 · 2022: 14 · 2021: 24 · 2020: 32 · 2019: 31 · 2018: 26 · 2017: 21 · 2016: 36 · 2015: 29 · 2014: 35 · 2013: 36 · 2012: 45
- FWCI
- 19.37
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- American Cancer Society
- National Institutes of Health (2r01ar050452-21)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR027883, R01 AR27883, R37AR027883, R01-AR050452)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Skin and Cellular Biology Research
- Keywords
- asymmetric cell division, Notch signaling, epidermal differentiation, epidermal stratification, spindle orientation, lateral geniculate nucleus, NUMA, dynactin, DCTN1, skin development, basal progenitor cells, cell polarity, skin barrier formation
- MeSH terms
- Dynactin Complex, Epidermal Cells, Animals, Carrier Proteins, Cell Differentiation, Cell Division, Cells, Cultured, Female, Male, Microtubule-Associated Proteins, Spindle Apparatus, Nuclear Proteins, Skin, Signal Transduction, Keratinocytes, Cell Cycle Proteins, Mice, Receptors, Notch, Gene Knockdown Techniques
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