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Differential RET signaling pathways drive development of the enteric lymphoid and nervous systems.

Patel, Amisha, Harker, Nicola, Moreira-Santos, Lara, Ferreira, Manuela, Alden, Keiran, Timmis, Jonathan, Foster, Katie, Garefalaki, Anna, Pachnis, Vassilis, Andrews, Paul, Enomoto, Hideki, Milbrandt, Jeffrey and Veiga-Fernandes, Henrique (2012) Differential RET signaling pathways drive development of the enteric lymphoid and nervous systems. Science signaling, 5 (235). ISSN 1945-0877

Item Type: Article

Abstract

During the early development of the gastrointestinal tract, signaling through the receptor tyrosine kinase RET is required for initiation of lymphoid organ (Peyer’s patch) formation and for intestinal innervation by enteric neurons. RET signaling occurs through glial cell line–derived neurotrophic factor (GDNF) family receptor α co-receptors present in the same cell (signaling in cis). It is unclear whether RET signaling in trans, which occurs in vitro through co-receptors from other cells, has a biological role. We showed that the initial aggregation of hematopoietic cells to form lymphoid clusters occurred in a RET-dependent, chemokine-independent manner through adhesion-mediated arrest of lymphoid tissue initiator (LTin) cells. Lymphoid tissue inducer cells were not necessary for this initiation phase. LTin cells responded to all RET ligands in trans, requiring factors from other cells, whereas RET was activated in enteric neurons exclusively by GDNF in cis. Furthermore, genetic and molecular approaches revealed that the versatile RET responses in LTin cells were determined by distinct patterns of expression of the genes encoding RET and its co-receptors. Our study shows that a trans RET response in LTin cells determines the initial phase of enteric lymphoid organ morphogenesis, and suggests that differential co-expression of Ret and Gfra can control the specificity of RET signaling.

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More Information

Depositing User: Jonathan Timmis

Identifiers

Item ID: 11630
Identification Number: https://doi.org/10.1126/scisignal.2002734
ISSN: 1945-0877
URI: http://sure.sunderland.ac.uk/id/eprint/11630
Official URL: https://stke.sciencemag.org/content/5/235/ra55.lon...

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Catalogue record

Date Deposited: 27 Feb 2020 14:43
Last Modified: 27 Feb 2020 14:43

Contributors

Author: Amisha Patel
Author: Nicola Harker
Author: Lara Moreira-Santos
Author: Manuela Ferreira
Author: Keiran Alden
Author: Jonathan Timmis
Author: Katie Foster
Author: Anna Garefalaki
Author: Vassilis Pachnis
Author: Paul Andrews
Author: Hideki Enomoto
Author: Jeffrey Milbrandt
Author: Henrique Veiga-Fernandes

University Divisions

Faculty of Technology > School of Computer Science

Subjects

Computing > Data Science
Sciences > Biomedical Sciences

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