Sci. Signal., 31 July 2012
RET Signaling in Cis and TransDevelopment of the enteric (gastrointestinal) organs requires coordinated growth of tissues from various embryonic layers. Evidence suggests that ligands of the receptor tyrosine kinase RET are used in different tissues to control distinct developmental end points. Lymphoid tissue initiator (LTin) cells are thought to function in the early development of Peyers patches (PPs), which are secondary lymphoid organs of the gut important for mucosal immunity. The formation of the enteric nervous system, which enervates the lymphoid tissue, depends on interactions between neural crest cells and stroma cells of the gut wall. RET signaling requires the presence of co-receptors, which bind to ligands, in the same cell (in cis), or RET co-receptors can be cleaved from cells, leading to the possibility of RET signaling in trans; however, the physiological relevance of such signaling is uncertain. Patel et al. investigated lymphoid tissue morphogenesis in mice and found that whereas development of the enteric nervous tissue depended on RET signaling in cis, aggregation of LTin cells and development of lymphoid tissue were driven by RET signaling in trans and depended on the local availability of RET co-receptors and ligands.
Citation: A. Patel, N. Harker, L. Moreira-Santos, M. Ferreira, K. Alden, J. Timmis, K. Foster, A. Garefalaki, P. Pachnis, P. Andrews, H. Enomoto, J. Milbrandt, V. Pachnis, M. C. Coles, D. Kioussis, H. Veiga-Fernandes, Differential RET Signaling Pathways Drive Development of the Enteric Lymphoid and Nervous Systems. Sci. Signal. 5, ra55 (2012).
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