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Publication : RET/GFRα signals are dispensable for thymic T cell development in vivo.

First Author  Almeida AR Year  2012
Journal  PLoS One Volume  7
Issue  12 Pages  e52949
PubMed ID  23300832 Mgi Jnum  J:195828
Mgi Id  MGI:5485334 Doi  10.1371/journal.pone.0052949
Citation  Almeida AR, et al. (2012) RET/GFRalpha signals are dispensable for thymic T cell development in vivo. PLoS One 7(12):e52949
abstractText  Identification of thymocyte regulators is a central issue in T cell biology. Interestingly, growing evidence indicates that common key molecules control neuronal and immune cell functions. The neurotrophic factor receptor RET mediates critical functions in foetal hematopoietic subsets, thus raising the possibility that RET-related molecules may also control T cell development. We show that Ret, Gfra1 and Gfra2 are abundantly expressed by foetal and adult immature DN thymocytes. Despite the developmentally regulated expression of these genes, analysis of foetal thymi from Gfra1, Gfra2 or Ret deficient embryos revealed that these molecules are dispensable for foetal T cell development. Furthermore, analysis of RET gain of function and Ret conditional knockout mice showed that RET is also unnecessary for adult thymopoiesis. Finally, competitive thymic reconstitution assays indicated that Ret deficient thymocytes maintained their differentiation fitness even in stringent developmental conditions. Thus, our data demonstrate that RET/GFRalpha signals are dispensable for thymic T cell development in vivo, indicating that pharmacological targeting of RET signalling in tumours is not likely to result in T cell production failure.
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