title: RET/GFRα signals are dispensable for thymic T cell development in vivo.
abstract: 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/GFRα 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.
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Lisboa, Portugal.
authors.forename: Afonso Rocha Martins
authors.initials: AR
authors.lastname: Almeida
authors.forename: Sílvia
authors.initials: S
authors.lastname: Arroz-Madeira
authors.forename: Diogo
authors.initials: D
authors.lastname: Fonseca-Pereira
authors.forename: Hélder
authors.initials: H
authors.lastname: Ribeiro
authors.forename: Reena
authors.initials: R
authors.lastname: Lasrado
authors.forename: Vassilis
authors.initials: V
authors.lastname: Pachnis
authors.forename: Henrique
authors.initials: H
authors.lastname: Veiga-Fernandes
mesh_terms: D000818:Animals; D018507:Gene Expression Regulation, Developmental; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013601:T-Lymphocytes / Q000378:metabolism*; D013950:Thymus Gland / Q000378:metabolism
chemical_list: C494990:GFRA2 protein, human; C494988:Gfra1 protein, mouse; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D051096:Proto-Oncogene Proteins c-ret; C494999:Ret protein, mouse