Molecular Neurogenetics

Genetic and molecular basis of proliferation of neural progenitor cells:

Neural cells in the adult brain arise from a small number of founder progenitor cells. These progenitor cells go through complex processes of proliferation and specification to yield the large number and diversity of neuronal and glial cells. Our goal is to identify genes and unraveling the molecular mechanisms underlying these processes. For this purpose we are using the brain proliferative center of Drosophila larvae (Ceron et al, Dev Biol, 2001; Ceron et al, Eur J.Cell Biol. 2006; Colonques et al,Mech, Devel.2007)) and the developing spinal cord of the chick embryo (Hammerle et al, Dev Biol. 2002;Hamerle and Tejedor,PLoS ONE,2007) as an experimental model. Thus, we have formerly cloned and characterized the Minibrain (Mnb) gene of Drosophila, which encodes a new protein kinase involved in postembryonic neurogenesis (Tejedor et al, Neuron, 1995). Mnb kinases are very well conserved throughout evolution and exhibit unique structural and biochemical properties (Becker et al, J Biol Chem, 1998). We are studying the diverse roles of Mnb in brain development (Hammerle et al, Dev Biol. 2002; Hammerle et al, Eur J Neurosci, 2003).

Molecular Basis of the involvement of Minibrain on Down Syndrome neuropathologies:

Down Syndrome (DS) generates a number neuropathological disorders that make it the leading cause of mental retardation. Based on genetic studies, a minimal critical region has been map on chromosome 21. Interestingly, the human Mnb orthologue is harbored within this region and is overexpressed in DS embryonic brain. On the basis of this genetic data together with the role of Mnb on brain development (Tejedor et al, Neuron, 1995; Hammerle et al, Dev Biol. 2002; Hammerle et al, Eur J Neurosci, 2003), we are investigating the possible involvement of Mnb on the neural alterations associated to Down Syndrome.

Our work has been supported by grants from the Fundación La Caixa, Fundación Mafre-Medicina, FundaciÓn Inocente Inocente, Fundacion AsinDown, Generalitat Valenciana, the Ministry of Science and Tecnology, the Ministry of Education and Science, AEI/FEDER; and Fondation Jérôme Lejeune.