Project: Central regulation of neuroendocrine functions, genomics and evolution

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Involvement of the MCH/MCHR1-MCHR2 system in the regulation of neuroendocrine functions

Our preferred model is that of the MCH peptide whose main function concerns the initiation of feeding behavior. The identification of a family of genes derived from the MCH gene only in primates has made it possible to initiate a vast research project aimed at understanding how the appearance of "primate-specific" genes could have influenced the emergence of new behaviors, particularly in the human lineage.
Unlike rodents (rat, mouse), two MCH receptors have been identified in humans. We have produced a transgenic mouse line expressing the human MCHR2 receptor (KI-hMCHR2 mouse). Functional characterization of the transgene is ongoing and should lead to the first detailed phenotypic analysis in a "humanized" mouse model for the MCH/MCHR1-MCHR2 system.

Study of the appearance and functional characterization of MCH-derived genes

A detailed study using molecular biology, phylogenetic and bioinformatics analysis techniques allowed us to propose an original scenario of the appearance of new genes derived from the MCH gene (PMCHL1/PMCHL2) selectively in the Hominoid lineage. Other genes with similar characteristics were identified in regions defined as "gene nurseries". The expression of these new "chimeric" genes is highly regulated in the human brain.
One of our main objectives is to reveal the functions of these genes in higher primates. We are also looking for a possible association between the expression of "primate-specific" genes and the etiology of metabolic diseases, such as obesity or anorexia, and neurodegenerative diseases, such as Parkinson's disease. In this context, we have recently found a gene expression "signature" in the cortex associated with disease progression in a monkey model and in Parkinsonian patients.