Resnik-Docampo_2017_Nat.Cell.Biol_19_52

Reference

Title : Tricellular junctions regulate intestinal stem cell behaviour to maintain homeostasis - Resnik-Docampo_2017_Nat.Cell.Biol_19_52
Author(s) : Resnik-Docampo M , Koehler CL , Clark RI , Schinaman JM , Sauer V , Wong DM , Lewis S , D'Alterio C , Walker DW , Jones DL
Ref : Nat Cell Biol , 19 :52 , 2017
Abstract :

Ageing results in loss of tissue homeostasis across taxa. In the intestine of Drosophila melanogaster, ageing is correlated with an increase in intestinal stem cell (ISC) proliferation, a block in terminal differentiation of progenitor cells, activation of inflammatory pathways, and increased intestinal permeability. However, causal relationships between these phenotypes remain unclear. Here, we demonstrate that ageing results in altered localization and expression of septate junction proteins in the posterior midgut, which is quite pronounced in differentiated enterocytes (ECs) at tricellular junctions (TCJs). Acute loss of the TCJ protein Gliotactin (Gli) in ECs results in increased ISC proliferation and a block in differentiation in intestines from young flies, demonstrating that compromised TCJ function is sufficient to alter ISC behaviour in a non-autonomous manner. Blocking the Jun N-terminal kinase signalling pathway is sufficient to suppress changes in ISC behaviour, but has no effect on loss of intestinal barrier function, as a consequence of Gli depletion. Our work demonstrates a pivotal link between TCJs, stem cell behaviour, and intestinal homeostasis and provides insights into causes of age-onset and gastrointestinal diseases.

PubMedSearch : Resnik-Docampo_2017_Nat.Cell.Biol_19_52
PubMedID: 27992405

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Citations formats

Resnik-Docampo M, Koehler CL, Clark RI, Schinaman JM, Sauer V, Wong DM, Lewis S, D'Alterio C, Walker DW, Jones DL (2017)
Tricellular junctions regulate intestinal stem cell behaviour to maintain homeostasis
Nat Cell Biol 19 :52

Resnik-Docampo M, Koehler CL, Clark RI, Schinaman JM, Sauer V, Wong DM, Lewis S, D'Alterio C, Walker DW, Jones DL (2017)
Nat Cell Biol 19 :52