RET/GFRα Signals Are Dispensable for Thymic T Cell Development <em>In Vivo</em>

<div><p>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 <em>Ret</em>, <em>Gfra1</em> and <em>Gfra2</em> are abundantly expressed by foetal and adult immature DN thymocytes. Despite the developmentally regulated expression of these genes, analysis of foetal thymi from <em>Gfra1</em>, <em>Gfra2</em> or <em>Ret</em> deficient embryos revealed that these molecules are dispensable for foetal T cell development. Furthermore, analysis of RET gain of function and <em>Ret</em> conditional knockout mice showed that RET is also unnecessary for adult thymopoiesis. Finally, competitive thymic reconstitution assays indicated that <em>Ret</em> deficient thymocytes maintained their differentiation fitness even in stringent developmental conditions. Thus, our data demonstrate that RET/GFRα signals are dispensable for thymic T cell development <em>in vivo</em>, indicating that pharmacological targeting of RET signalling in tumours is not likely to result in T cell production failure.</p>