UNCDOPA · Dopaminergic cell fate determinants in C. elegans: characterization of Unc-86 as a general repressor of dopaminergic differentiation
FP6 — Marie Curie Actions (Human Resources and Mobility)
- Duration
- 2007-03-01 → 2010-02-28
- EU contribution
- €250,744
- Participants
- 2
- Scheme
- OIF
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Project objective
Dopaminergic (DA) neurons play a central role in the coordination of movement, neuroendocrine function, attention, cognition, emotion, memory and reward. In addition, the DA system has been extensively studied because its dysfunction is linked to various pathological conditions including Parkinson's disease. The extraordinary complexity of the mammalian brain has limited our ability to dissect the regulatory machinery involved in DA differentiation.However, the many fundamental similarities between the mammalian and invertebrate nervous system, together with the simplicity of C. elegans, make this species an ideal model for forward genetic mutant analysis. As in mammals, very little is still known about DA differentiation in worms. Loss of function of Unc-8 6 transcription factor leads to increased numbers of DA neurons, suggesting a role for Unc-86 as a DA fate repressor.The study of Unc-86 mutants would allow us to increase our knowledge about the molecular mechanisms involved in DA differentiation. In this project I will characterize the extent to which Unc-86 inhibits DA fate, that is, if Unc-86 works as a global DA fate repressor in all DA lineages. I will also characterize if Unc-86 acts as a repressor or an activator of other transcription factors. Finally, I will perform a genetic screening to identify new genes that cooperate with Unc-86 to repress DA fate.As we begin to understand the function of specific genes in DA differentiation, we may be able to formulate hypotheses about their significance as candidates associated to dopamine-related mental disorders. This knowledge should also become the basis to design new and more efficient strategies to manipulate dopamine neurons in PD therapies.
Original text from CORDIS.
Participants
- CENTRE DE REGULACIÓ GENÒMICA · BARCELONACoordinatorCity levelSpain
- COLUMBIA UNIVERSITY MEDICAL CENTER. HOWARD HUGHES MEDICAL INSTITUTE · NEW YORKCity levelUnited States
Links
Data: CORDIS, © European Union