Elsevier

Developmental Biology

Volume 377, Issue 1, 1 May 2013, Pages 177-187
Developmental Biology

Integrin signaling is required for maintenance and proliferation of intestinal stem cells in Drosophila

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Abstract

Tissue-specific stem cells are maintained by both local secreted signals and cell adhesion molecules that position the stem cells in the niche microenvironment. In the Drosophila midgut, multipotent intestinal stem cells (ISCs) are located basally along a thin layer of basement membrane that composed of extracellular matrix (ECM), which separates ISCs from the surrounding visceral musculature: the muscle cells constitute a regulatory niche for ISCs by producing multiple secreted signals that directly regulate ISC maintenance and proliferation. Here we show that integrin-mediated cell adhesion, which connects the ECM and intracellular cytoskeleton, is required for ISC anchorage to the basement membrane. Specifically, the α-integrin subunits including αPS1 encoded by mew and αPS3 encoded by scb, and the β-integrin subunit encoded by mys are richly expressed in ISCs and are required for the maintenance, rather than their survival or multiple lineage differentiation. Furthermore, ISC maintenance also requires the intercellular and intracellular integrin signaling components including Talin, Integrin-linked kinase (Ilk), and the ligand, Laminin A. Notably, integrin mutant ISCs are also less proliferative, and genetic interaction studies suggest that proper integrin signaling is a pre-requisite for ISC proliferation in response to various proliferative signals and for the initiation of intestinal hyperplasia after loss of adenomatous polyposis coli (Apc). Our studies suggest that integrin not only functions to anchor ISCs to the basement membrane, but also serves as an essential element for ISC proliferation during normal homeostasis and in response to oncogenic mutations.

Highlights

► The function of Integrin signaling in fly intestinal stem cells was investigated. ► αPS1 (mew),αPS3(scb) and βPS (mys) are expressed in ISCs for maintenance. ► Integrin signaling is required for ISC proliferation but not survival. ► Disruption of integrin triggers cell cycle arrest and prevents tumorigenesis.

Keywords

Integrin
Intestinal stem cell
Niche
Maintenance
Proliferation
Basement membrane
Drosophila
Tumorigenesis

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