Cited by 406Developmental Biology and Gene RegulationMicrotubule and mitosis dynamicsSkin and Cellular Biology Research

Asymmetric cell divisions promote Notch-dependent epidermal differentiation

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Williams, Scott E., Beronja, Slobodan, Pasolli, H. Amalia, Fuchs, Elaine·2011·Nature

Abstract

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 interfollicular epidermis and hair follicles.

    “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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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
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
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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