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Hippo-YAP/TAZ 通路对骨骼形态发生的控制。

Control of skeletal morphogenesis by the Hippo-YAP/TAZ pathway.

机构信息

The Francis Crick Institute, 1 Midland Rd, St Pancras, NW1 1AT London, UK.

The Francis Crick Institute, 1 Midland Rd, St Pancras, NW1 1AT London, UK

出版信息

Development. 2020 Nov 12;147(21):dev187187. doi: 10.1242/dev.187187.

DOI:10.1242/dev.187187
PMID:32994166
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7673359/
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, , / double knockout impairs murine chondrocyte proliferation, whereas constitutively nuclear accelerates proliferation, in line with the canonical role of this pathway in most tissues. However, , cartilage-specific knockout of / does not prevent chondrocyte proliferation, differentiation or skeletal growth, but rather results in various skeletal deformities including cleft palate. Cartilage-specific expression of or knockout of / do not increase cartilage growth, but instead lead to catastrophic malformations resembling chondrodysplasia or achondrogenesis. Physiological YAP target genes in cartilage include , and several matrix remodelling enzymes. Thus, YAP/TAZ activity controls chondrocyte proliferation , possibly reflecting a regenerative response, but is dispensable for chondrocyte proliferation , and instead functions to control cartilage morphogenesis via regulation of the extracellular matrix.

摘要

Hippo-YAP/TAZ 通路是组织生长的重要调节剂，但也可以控制细胞命运或组织形态发生。在这里，我们研究了 Hippo 通路在软骨发育过程中的功能，软骨构成了大部分骨骼。此前，YAP 通过抑制软骨细胞增殖和分化来抑制骨骼生长。我们发现，在大多数组织中， / 双敲除会损害小鼠软骨细胞的增殖，而持续核定位的 YAP 则会加速增殖，这与该通路的典型作用一致。然而，软骨特异性的 / 敲除并不能阻止软骨细胞的增殖、分化或骨骼生长，反而会导致各种骨骼畸形，包括腭裂。软骨特异性表达 或 / 敲除并不会增加软骨生长，反而会导致类似于软骨发育不全或软骨生成不全的灾难性畸形。软骨中的生理 YAP 靶基因包括 、 和几种基质重塑酶。因此，YAP/TAZ 活性控制软骨细胞增殖，可能反映了一种再生反应，但对于软骨细胞增殖是可有可无的，而是通过调节细胞外基质来控制软骨形态发生。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4280/7673359/b9e13f46da50/develop-147-187187-g7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4280/7673359/a120053801ba/develop-147-187187-g1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4280/7673359/d2eb9b2cb2b8/develop-147-187187-g2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4280/7673359/6249d5136f85/develop-147-187187-g3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4280/7673359/7d84ada13d63/develop-147-187187-g4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4280/7673359/3d2c89a14710/develop-147-187187-g5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4280/7673359/a91bef52717e/develop-147-187187-g6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4280/7673359/b9e13f46da50/develop-147-187187-g7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4280/7673359/a120053801ba/develop-147-187187-g1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4280/7673359/d2eb9b2cb2b8/develop-147-187187-g2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4280/7673359/6249d5136f85/develop-147-187187-g3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4280/7673359/7d84ada13d63/develop-147-187187-g4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4280/7673359/3d2c89a14710/develop-147-187187-g5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4280/7673359/a91bef52717e/develop-147-187187-g6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4280/7673359/b9e13f46da50/develop-147-187187-g7.jpg

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