Research objectives and content
The number of transcription factors with known discrete temporal patterns of regional and cell type specific expression in the developing vertebrate nervous system is rapidly increasing. The aim of this research project is to determine the properties and role of a new homeobox gene named X3 that has been cloned from rat brain in the host institution, in the development and maintenance of the mesencephalic dopaminergic system. The following studies will provide critical insights in X3 function during regionalization and cell-fate specification in the nervous system, and will be very useful to understand the molecular mechanisms regulating vertebrate neural development and degeneration or misdevelopment of the mesencephalic dopaminergic system, which relates to neurological and psychiatric diseases like maniac depression, schizophrenia and Parkinson disease. The proposed research plan focuses on several aspects of the X3 gene: It will determine the temporal relationship of expression of X3 and Nurrl (whose loss of expression causes agenesis of the mesDA system in mice). It will determine the transactivating and DNA binding properties of X3 on promoters of genes expressed in the mesDA, as well as its possible functional interaction with Nurrl. Its functional properties will be tested in knockout mice (ongoing project).
Training content (objective, benefit and expected impact)
The development of the present research project will allow the applicant to learn new techniques and acquire fresh knowledge in a field completely different from the previous studies realized during the PhD studies. Specifically, the results obtained from the proposed project on X3, may be exploited for manipulation of dopaminergic cells in vitro, in preparation of grafting, an experimental therapy for Parkinson patients. Links with industry / industrial relevance (22)