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Lats1 and Lats2 are required for the maintenance of multipotency in the Müllerian duct mesenchyme
Author(s) -
G St-Jean,
Mayra Tsoi,
Atefeh Abedini,
Adrien Levasseur,
Charlène Rico,
Martin Morin,
Bojana Djordjevic,
Ilkka Miinalainen,
Riitta Kaarteenaho,
Marilène Paquet,
Nicolas Gévry,
Alexandre Boyer,
Barbara C. Vanderhyden,
Derek Boerboom
Publication year - 2019
Publication title -
development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.15
H-Index - 36
eISSN - 1477-9129
pISSN - 0950-1991
DOI - 10.1242/dev.180430
Subject(s) - biology , hippo signaling pathway , mesenchyme , microbiology and biotechnology , wnt signaling pathway , mesoderm , intermediate mesoderm , yap1 , myofibroblast , mesenchymal stem cell , signal transduction , genetics , medicine , embryonic stem cell , embryo , transcription factor , embryogenesis , fibrosis , gastrulation , gene
WNT signaling plays essential roles in the development and function of the female reproductive tract. Although crosstalk with the Hippo pathway is a key regulator of WNT signaling, whether Hippo itself plays a role in female reproductive biology remains largely unknown. In this report, we show that conditional deletion of the key Hippo kinases Lats1 and Lats2 in Müllerian duct mesenchyme cells caused them to adopt the myofibroblast cell fate, resulting in profound reproductive tract developmental defects and sterility. Myofibroblast differentiation was attributed to increased YAP and TAZ expression (but not to altered WNT signaling), leading to the direct transcriptional up-regulation of Ctgf and the activation of the myofibroblast genetic program. Müllerian duct mesenchyme cells also became myofibroblasts in male mutant embryos, which impeded the development of the male reproductive tract and resulted in cryptorchidism. The inactivation of Lats1/2 in differentiated uterine stromal cells in vitro did not compromise their ability to decidualize, suggesting that Hippo is dispensable during implantation. We conclude that Hippo signaling is required to suppress the myofibroblast genetic program and maintain multipotency in Müllerian mesenchyme cells.

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