PAR-4/LKB1 prevents intestinal hyperplasia by restricting endoderm specification in C. elegans embryos - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Development (Cambridge, England) Année : 2024

PAR-4/LKB1 prevents intestinal hyperplasia by restricting endoderm specification in C. elegans embryos

Résumé

The kinase PAR-4/LKB1 is a major regulator of intestinal homeostasis, which prevents polyposis in humans. Moreover, its ectopic activation is sufficient to induce polarization and formation of microvilli-like structures in intestinal cell lines. Here, we use Caenorhabditis elegans to examine the role of PAR-4 during intestinal development in vivo. We show that it is not required to establish enterocyte polarity and plays only a minor role in brush border formation. By contrast, par-4 mutants display severe deformations of the intestinal lumen as well as supernumerary intestinal cells, thereby revealing a previously unappreciated function of PAR-4 in preventing intestinal hyperplasia. The presence of supernumerary enterocytes in par-4 mutants is not due to excessive cell proliferation, but rather to the abnormal expression of the intestinal cell fate factors end-1 and elt-2 outside the E lineage. Notably, par-4 mutants also display reduced expression of end-1 and elt-2 inside the E lineage. Our work thereby unveils an essential and dual role of PAR-4, which both restricts intestinal specification to the E lineage and ensures its robust differentiation.

Domaines

Génétique
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jeudi 4 juillet 2024
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Dates et versions

hal-04342826 , version 1 (08-04-2024)

Licence

Paternité - Pas d'utilisation commerciale

Identifiants

Citer

Flora Demouchy, Ophélie Nicolle, Grégoire Michaux, Anne Pacquelet. PAR-4/LKB1 prevents intestinal hyperplasia by restricting endoderm specification in C. elegans embryos. Development (Cambridge, England), 2024, Development (cambridge, England), 151 (1), ⟨10.1242/dev.202205⟩. ⟨hal-04342826⟩
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