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Cdc42/N-WASP signaling links actin dynamics to pancreatic β cell delamination and differentiation.

Kesavan, Gokul LU ; Lieven, Oliver LU ; Mamidi, Anant LU ; Löf-Öhlin, Zarah LU ; Johansson, Jenny LU ; Li, Wan-Chun LU ; Lommel, Silvia; Greiner, Thomas LU and Semb, Henrik LU (2014) In Development 141(3). p.685-696
Abstract
Delamination plays a pivotal role during normal development and cancer. Previous work has demonstrated that delamination and epithelial cell movement within the plane of an epithelium are associated with a change in cellular phenotype. However, how this positional change is linked to differentiation remains unknown. Using the developing mouse pancreas as a model system, we show that β cell delamination and differentiation are two independent events, which are controlled by Cdc42/N-WASP signaling. Specifically, we show that expression of constitutively active Cdc42 in β cells inhibits β cell delamination and differentiation. These processes are normally associated with junctional actin and cell-cell junction disassembly and the expression... (More)
Delamination plays a pivotal role during normal development and cancer. Previous work has demonstrated that delamination and epithelial cell movement within the plane of an epithelium are associated with a change in cellular phenotype. However, how this positional change is linked to differentiation remains unknown. Using the developing mouse pancreas as a model system, we show that β cell delamination and differentiation are two independent events, which are controlled by Cdc42/N-WASP signaling. Specifically, we show that expression of constitutively active Cdc42 in β cells inhibits β cell delamination and differentiation. These processes are normally associated with junctional actin and cell-cell junction disassembly and the expression of fate-determining transcription factors, such as Isl1 and MafA. Mechanistically, we demonstrate that genetic ablation of N-WASP in β cells expressing constitutively active Cdc42 partially restores both delamination and β cell differentiation. These findings elucidate how junctional actin dynamics via Cdc42/N-WASP signaling cell-autonomously control not only epithelial delamination but also cell differentiation during mammalian organogenesis. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Development
volume
141
issue
3
pages
685 - 696
publisher
Society for International Development
external identifiers
  • pmid:24449844
  • wos:000330573500019
  • scopus:84892718794
ISSN
1477-9129
DOI
10.1242/dev.100297
language
English
LU publication?
yes
id
2c515803-1ddf-4014-b0ef-eb19fb7bb947 (old id 4290880)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24449844?dopt=Abstract
date added to LUP
2014-02-07 14:39:03
date last changed
2017-11-19 03:22:08
@article{2c515803-1ddf-4014-b0ef-eb19fb7bb947,
  abstract     = {Delamination plays a pivotal role during normal development and cancer. Previous work has demonstrated that delamination and epithelial cell movement within the plane of an epithelium are associated with a change in cellular phenotype. However, how this positional change is linked to differentiation remains unknown. Using the developing mouse pancreas as a model system, we show that β cell delamination and differentiation are two independent events, which are controlled by Cdc42/N-WASP signaling. Specifically, we show that expression of constitutively active Cdc42 in β cells inhibits β cell delamination and differentiation. These processes are normally associated with junctional actin and cell-cell junction disassembly and the expression of fate-determining transcription factors, such as Isl1 and MafA. Mechanistically, we demonstrate that genetic ablation of N-WASP in β cells expressing constitutively active Cdc42 partially restores both delamination and β cell differentiation. These findings elucidate how junctional actin dynamics via Cdc42/N-WASP signaling cell-autonomously control not only epithelial delamination but also cell differentiation during mammalian organogenesis.},
  author       = {Kesavan, Gokul and Lieven, Oliver and Mamidi, Anant and Löf-Öhlin, Zarah and Johansson, Jenny and Li, Wan-Chun and Lommel, Silvia and Greiner, Thomas and Semb, Henrik},
  issn         = {1477-9129},
  language     = {eng},
  number       = {3},
  pages        = {685--696},
  publisher    = {Society for International Development},
  series       = {Development},
  title        = {Cdc42/N-WASP signaling links actin dynamics to pancreatic β cell delamination and differentiation.},
  url          = {http://dx.doi.org/10.1242/dev.100297},
  volume       = {141},
  year         = {2014},
}