Collagen 18 and agrin are secreted by enteric neural crest cells to remodel their microenvironment and regulate their migration during ENS development

Abstract

The enteric nervous system (ENS) arises from neural crest cells that migrate, proliferate, and differentiate into enteric neurons and glia within the intestinal wall. Many extracellular matrix (ECM) components are present in the embryonic gut, but their role in regulating ENS development is largely unknown. Here, we identify heparan sulfate proteoglycan proteins, including collagen XVIII (Col18) and agrin, as important regulators of enteric neural crest-derived cell (ENCDC) development. In developing avian hindgut, Col18 is expressed at the ENCDC wavefront, while agrin expression occurs later. Both proteins are normally present around enteric ganglia, but are absent in aganglionic gut. Using chick-mouse intestinal chimeras and enteric neurospheres, we show that vagal- and sacral-derived ENCDCs from both species secrete Col18 and agrin. Whereas glia express Col18 and agrin, enteric neurons only express the latter. Functional studies demonstrate that Col18 is permissive whereas agrin is strongly inhibitory to ENCDC migration, consistent with the timing of their expression during ENS development. We conclude that ENCDCs govern their own migration by actively remodeling their microenvironment through secretion of ECM proteins.

Intraganglionic macrophages: a new population of cells in the enteric ganglia

“…4D, Supporting Information Video S1). Agrin expression delineates the outer border of the enteric ganglia, as recently shown in mouse and chicken (Nagy et al 2018). The CX3CR1 GFP cells present within the myenteric ganglia have a highly ramified appearance and express CD45 ( Fig.…”

The Role of the Extracellular Matrix and Its Molecular and Cellular Regulators in Cancer Cell Plasticity

“…The mechanical properties of the newly synthesized ECM are an important determinant of how quickly the wound heals ( 23 ). Similarly, the ECM is set down early in embryonic development and influences the delamination, migration and differentiation at their destination of diverse cell types ( 24 , 25 ). Since the physiological functions and behaviors of normal cell types and strongly influenced by the normal ECM, it is no surprise that similarly the tumor ECM exerts a strong influence on the behavior or cancer cells.…”

Az intestinalis macrophagok és az enteralis idegrendszer szerepe a bél neuroimmunológiai kapcsolataiban. Alapkutatás és klinikai vonatkozások

“…A bevezetőben említett intraganglionaris macrophagok (IM) egy MM-populációt képeznek, és sejttestükkel a myentericus plexus enteralis ganglionjait körülvevő extracelluláris mátrix tokján belül [8], a neuronok és a gliasejtek között helyezkednek el [7]. Habár a MyM-ok között jellemzőek olyan sejtek, melyek sejtteste a ganglionokon kívül fordul elő, de nyúlványaikkal beérnek az idegdúcok belsejébe (periganglionaris macrophagok), olyan haemopoeticus sejt, mely teljes egészében a ganglionok idegszöveti mikrokörnyezetében helyezkedik el, eddig nem került leírásra.…”

“…Ezek a megfigyelések felvetették annak lehetőségét, hogy az enteralis ganglionokban a ganglionléc-eredetű neuronokon és gliasejteken kívül egy harmadik sejtpopuláció is létezik. Ezek a haemopoeticus eredetű nyúlványos sejtek az enteralis neuronokat és gliát körbefonva, a ganglionokat a környezetüktől elhatároló extracelluláris mátrixban (ECM) gazdag tokon [8] belül helyezkednek el, és microgliára specifikus (MHCII, CSF1R, Iba1, CD11b, F4/80) sejtfelszíni markereket expresszálnak [7,9].…”