Skip to main content

Dissecting the gene regulatory mechanisms that generate serotonergic neurons and their link to mental disorders

Objective

Mental disorders constitute a human an economic burden for developed countries. Many mental disorders are linked to serotonin dysfunction, but the exact mechanism underlying these disorders is not well understood. Serotonin Related Mental Disorders (SRMD) are multigenic, making the identification of these mechanisms a difficult task. Understanding the molecular mechanisms that generate serotonergic neurons will provide us with the tools to identify mutations that could predispose to SRMD. In this grant we will use a multidisciplinary approach to dissect the transcriptional mechanisms that generate serotonergic neurons and use this knowledge to identify genetic links to SRMD. Serotonergic neurons are very ancient in evolution and enzymes and transporters responsible for the production of serotonin (serotonin pathway genes) are very well conserved in all metazoans. We would take advantage of this evolutionary conservation and use the genetic amenability of C. elegans to dissect the genetic mechanisms responsible for the generation of the serotonergic neurons. We will apply the lessons learned from C. elegans to unravel analogous mechanisms regulating mouse serotonergic differentiation. Our preliminary results show that the serotonergic pathway genes are co-regulated by the same factors and that this mechanism is evolutionary conserved. We will identify the cis-acting sequences (serotonergic motif) and trans-acting factors responsible for the activation of the serotonergic features, both in worms and mice. Finally, we will apply our knowledge on serotonergic differentiation to identify genetic association to SRMDs. Mutations in the serotonergic motif could lead to defects on the expression of the serotonergic genes, resulting in a dysfunctional serotonergic neuron. We will build a database of all human serotonergic motifs and look for mutations in these sites in SRMD patients. In summary, this grant will give us the tools to better understand and treat SRMD.

Call for proposal

ERC-2011-StG_20101109
See other projects for this call

Host institution

AGENCIA ESTATAL CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS
Address
Calle Serrano 117
28006 Madrid
Spain
Activity type
Research Organisations
EU contribution
€ 1 931 621
Principal investigator
Nuria Flames Bonilla (Dr.)
Administrative Contact
Guillermo Sanjuanbenito García (Mr.)

Beneficiaries (1)

AGENCIA ESTATAL CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS
Spain
EU contribution
€ 1 931 621
Address
Calle Serrano 117
28006 Madrid
Activity type
Research Organisations
Principal investigator
Nuria Flames Bonilla (Dr.)
Administrative Contact
Guillermo Sanjuanbenito García (Mr.)