Regulated spindle orientation buffers tissue growth in the epidermis.
Animals
Asymmetric Cell Division
/ genetics
Cell Division
/ genetics
Cell Polarity
/ genetics
Cell Proliferation
/ genetics
Epidermal Cells
/ metabolism
Epidermis
/ growth & development
Homeostasis
/ genetics
Mice
Proto-Oncogene Proteins p21(ras)
/ genetics
Skin
/ growth & development
Spindle Apparatus
Stem Cells
/ cytology
Ras
cell biology
epidermis
homeostasis
mouse
oncogene
skin
spindle orientation
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
02 10 2019
02 10 2019
Historique:
received:
15
05
2019
accepted:
01
10
2019
pubmed:
3
10
2019
medline:
20
2
2020
entrez:
3
10
2019
Statut:
epublish
Résumé
Tissue homeostasis requires a balance between progenitor cell proliferation and loss. Mechanisms that maintain this robust balance are needed to avoid tissue loss or overgrowth. Here we demonstrate that regulation of spindle orientation/asymmetric cell divisions is one mechanism that is used to buffer changes in proliferation and tissue turnover in mammalian skin. Genetic and pharmacologic experiments demonstrate that asymmetric cell divisions were increased in hyperproliferative conditions and decreased under hypoproliferative conditions. Further, active K-Ras also increased the frequency of asymmetric cell divisions. Disruption of spindle orientation in combination with constitutively active K-Ras resulted in massive tissue overgrowth. Together, these data highlight the essential roles of spindle orientation in buffering tissue homeostasis in response to perturbations.
Identifiants
pubmed: 31577227
doi: 10.7554/eLife.48482
pii: 48482
pmc: PMC6794086
doi:
pii:
Substances chimiques
Hras protein, mouse
EC 3.6.5.2
Proto-Oncogene Proteins p21(ras)
EC 3.6.5.2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NICHD NIH HHS
ID : T32 HD040372
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR067203
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01AR055926
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01AR067203
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR055926
Pays : United States
Informations de copyright
© 2019, Morrow et al.
Déclaration de conflit d'intérêts
AM, JU, LS, TH, TL No competing interests declared
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