Cdc42/N-WASP signaling links actin dynamics to pancreatic β cell delamination and differentiation.
(2014) In Development: For advances in developmental biology and stem cells 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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4290880
- author
- 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
- organization
- publishing date
- 2014
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Development: For advances in developmental biology and stem cells
- volume
- 141
- issue
- 3
- pages
- 685 - 696
- publisher
- The Company of Biologists Ltd
- 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
- 2016-04-01 11:06:52
- date last changed
- 2022-08-27 23:26:32
@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 = {{The Company of Biologists Ltd}},
series = {{Development: For advances in developmental biology and stem cells}},
title = {{Cdc42/N-WASP signaling links actin dynamics to pancreatic β cell delamination and differentiation.}},
url = {{http://dx.doi.org/10.1242/dev.100297}},
doi = {{10.1242/dev.100297}},
volume = {{141}},
year = {{2014}},
}