期刊
DEVELOPMENTAL CELL
卷 20, 期 5, 页码 583-596出版社
CELL PRESS
DOI: 10.1016/j.devcel.2011.03.013
关键词
-
资金
- Alex's Lemonade Stand Foundation
- Sidney Kimmel Foundation
- NCI [R37CA058596, P50CA101942]
- Howard Hughes Medical Institute
- Fonds de la Recherche en Sante du Quebec (FRSQ)
- Kidney Research Scientist Core Education and National Training Program (KRESCENT)
- NIDDK [K08DK080175]
- Burroughs Welcome Fund
- Massachusetts General Hospital
WTX is an X-linked tumor suppressor targeted by somatic mutations in Wilms tumor, a pediatric kidney cancer, and by germline inactivation in osteopathia striata with cranial sclerosis, a bone overgrowth syndrome. Here, we show that Wtx deletion in mice causes neonatal lethality, somatic overgrowth, and malformation of multiple mesenchyme-derived tissues, including bone, fat, kidney, heart, and spleen. Inactivation of Wtx at different developmental stages and in primary mesenchymal progenitor cells (MPCs) reveals that bone mass increase and adipose tissue deficiency are due to altered lineage fate decisions coupled with delayed terminal differentiation. Specification defects in MPCs result from aberrant beta-catenin activation, whereas alternative pathways contribute to the subsequently delayed differentiation of lineage-restricted cells. Thus, Wtx is a regulator of MPC commitment and differentiation with stage-specific functions in inhibiting canonical Wnt signaling. Furthermore, the constellation of anomalies in Wtx null mice suggests that this tumor suppressor broadly regulates MPCs in multiple tissues.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据