Control of skeletal morphogenesis by the Hippo-YAP/TAZ pathway
Journal Title
Development
Publication Type
Journal epub ahead of print
Abstract
The Hippo-YAP/TAZ pathway is an important regulator of tissue growth, but can also control cell fate or tissue morphogenesis. Here we investigate the function of the Hippo pathway during the development of cartilage, which forms the majority of the skeleton. Previously, YAP was proposed to inhibit skeletal size by repressing chondrocyte proliferation and differentiation. We find that, in vitro, Yap/Taz double knockout impairs chondrocyte proliferation, whilst constitutively nuclear nls-YAP5SA accelerates proliferation, in line with the canonical role of this pathway in most tissues. However, in vivo, cartilage-specific knockout of Yap/Taz does not prevent chondrocyte proliferation, differentiation, or skeletal growth, but rather results in various skeletal deformities including cleft palate. Cartilage-specific expression of nls-YAP5SA or knockout of Lats1/2 do not increase cartilage growth but instead lead to catastrophic malformations resembling chondrodysplasia or achondrogenesis. Physiological YAP target genes in cartilage include Ctgf, Cyr61 and several matrix remodelling enzymes. Thus, YAP/TAZ activity controls chondrocyte proliferation in vitro, possibly reflecting a regenerative response, but is dispensable for chondrocyte proliferation in vivo, and instead functions to control cartilage morphogenesis via regulation of the extracellular matrix.
Publisher
COB
Research Division(s)
Epigenetics And Development
PubMed ID
32994166
Open Access at Publisher's Site
https://doi.org/10.1242/dev.187187
Terms of Use/Rights Notice
Refer to copyright notice on published article.


Creation Date: 2020-10-02 02:01:51
Last Modified: 2020-10-02 02:44:33
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