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There are currently no treatments for salivary gland diseases, making it vital to understand signaling mechanisms operating in acinar and ductal cells so as to develop regenerative therapies. To date, little work has focused on elucidating the signaling cascades controlling the differentiation of these cell types in adult mammals. To analyze the function of the Hippo‐TAZ/YAP1 pathway in adult mouse salivary glands, we generated adMOB1DKO mice in which both MOB1A and MOB1B were TAM‐inducibly deleted when the animals were adults. Three weeks after TAM treatment, adMOB1DKO mice exhibited smaller submandibular glands (SMGs) than controls with a decreased number of acinar cells and an increased number of immature dysplastic ductal cells. The mutants suffered from reduced saliva production accompanied by mild inflammatory cell infiltration and fibrosis in SMGs, similar to the Sjogren's syndrome. MOB1‐deficient acinar cells showed normal proliferation and apoptosis but decreased differentiation, leading to an increase in acinar/ductal bilineage progenitor cells. These changes were TAZ‐dependent but YAP1‐independent. Biochemically, MOB1‐deficient salivary epithelial cells showed activation of the TAZ/YAP1 and β‐catenin in ductal cells, but reduced SOX2 and SOX10 expression in acinar cells. Thus, Hippo‐TAZ signaling is critical for proper ductal and acinar cell differentiation and function in adult mice. [ABSTRACT FROM AUTHOR]

Mammalian STE20‐like protein kinase 1/2 (MST1/2) and nuclear Dbf2‐related kinase 1/2 (NDR1/2) are core components of Hippo signaling that are also known to be important regulators of lymphocyte trafficking. However, little is understood about the roles of other Hippo pathway molecules in these cells. Here, we present the first analysis of the function of Mps one binder kinase activator‐1 (MOB1) in T lymphocytes in vivo. T‐cell‐specific double knockout (DKO) of MOB1A/B in mice [tMob1 DKO mice] reduces the number of naïve T cells in both the circulation and secondary lymphoid organs, but leads to an accumulation of CD4+CD8− and CD4−CD8+ single‐positive (SP) cells in the thymus. In vitro, naïve MOB1A/B‐deficient T cells show increased apoptosis and display impaired trafficking capacity in response to the chemokine CCL19. These defects are linked to suppression of the activation of MST and NDR kinases, but are independent of the downstream transcriptional co‐activator Yes‐associated protein 1 (YAP1). Thus, MOB1 proteins play an important role in thymic egress and T‐cell survival that is mediated by a pathway other than conventional Hippo‐YAP1 signaling. [ABSTRACT FROM AUTHOR]