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Dev Cell. 2011 May 17;20(5):583-596. doi: 10.1016/j.devcel.2011.03.013.

The WTX tumor suppressor regulates mesenchymal progenitor cell fate specification.

Author information

Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA.
Department of Pathology, Harvard Medical School, Boston, MA 02114, USA.
Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, MA 02115, USA.
Endocrine Unit, Harvard Medical School, Boston, MA 02114, USA.
Center for Regenerative Medicine, Harvard Medical School, Boston, MA 02114, USA.
Contributed equally

Erratum in

  • Dev Cell. 2012 May 15;22(5):1109-17.


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 β-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.

[Indexed for MEDLINE]
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