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Mesenchymal–epithelial interactions during digestive tract development and epithelial stem cell regeneration

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Abstract

The gastrointestinal tract develops from a simple and uniform tube into a complex organ with specific differentiation patterns along the anterior–posterior and dorso-ventral axes of asymmetry. It is derived from all three germ layers and their cross-talk is important for the regulated development of fetal and adult gastrointestinal structures and organs. Signals from the adjacent mesoderm are essential for the morphogenesis of the overlying epithelium. These mesenchymal–epithelial interactions govern the development and regionalization of the different gastrointestinal epithelia and involve most of the key morphogens and signaling pathways, such as the Hedgehog, BMPs, Notch, WNT, HOX, SOX and FOXF cascades. Moreover, the mechanisms underlying mesenchyme differentiation into smooth muscle cells influence the regionalization of the gastrointestinal epithelium through interactions with the enteric nervous system. In the neonatal and adult gastrointestinal tract, mesenchymal–epithelial interactions are essential for the maintenance of the epithelial regionalization and digestive epithelial homeostasis. Disruption of these interactions is also associated with bowel dysfunction potentially leading to epithelial tumor development. In this review, we will discuss various aspects of the mesenchymal–epithelial interactions observed during digestive epithelium development and differentiation and also during epithelial stem cell regeneration.

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Abbreviations

αSMA:

Alpha smooth muscle actin

AIP:

Anterior intestinal portal

AP:

Anterior-posterior

BMP:

Bone morphogenetic protein

CDX:

Caudal type homeobox

CIP:

Caudal intestinal portal

CRC:

Colorectal cancer

ECM:

Extracellular matrix

ENS:

Enteric nervous system

FGF:

Fibroblast growth factor

GAS1:

Growth arrest specific gene 1

GI:

Gastrointestinal

GSEMF:

Gastric subepithelial myofibroblast

IHH:

Indian hedgehog

ISEMF:

Intestinal subepithelial myofibroblast

miR:

microRNA

P-SMAD1:

Phosphorylated SMAD1/5/8

SHH:

Sonic hedgehog

SOX9:

Sry-containing box gene 9

SM22:

Smooth muscle protein 22

SMC:

Smooth muscle cell

TGF-β:

Transforming growth factor β

vENCC:

Vagal enteric neural crest cell

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Acknowledgments

The work in de Santa Barbara’s lab is supported by the Association pour la Recherche Contre le Cancer (ARC) foundation, the Association Française contre les Myopathies (AFM) and the French Patients’ Association POIC. LLG is supported by an ARC post-doctoral fellowship. PdSB thanks Drucilla Jane Roberts for her contribution in the field, inspiration and continuous support.

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  1. INSERM U1046, UMR CNRS 9214, Université de Montpellier, 34295, Montpellier, France

    Ludovic Le Guen, Stéphane Marchal, Sandrine Faure & Pascal de Santa Barbara

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Correspondence to Pascal de Santa Barbara.

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Le Guen, L., Marchal, S., Faure, S. et al. Mesenchymal–epithelial interactions during digestive tract development and epithelial stem cell regeneration. Cell. Mol. Life Sci. 72, 3883–3896 (2015). https://doi.org/10.1007/s00018-015-1975-2

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