Neurogenesis and Pattern Formation
During the development of the nervous system, the production of hundreds of subtypes of neurons and glia cells depends on the rapid generation, amplification, specification and differentiation of progenitors and neural stem cells (NSCs). This strategy is retained in certain niches of the adult nervous system throughout life under physiological conditions. However, in adults the process is much more restricted, both in the number and in the generated cell subtypes. Although the molecular mechanisms appear to be common between embryonic and adult neurogenesis, it is unclear how it is possible to produce different growth rates in different periods of time.
Our group has shown that transcription factors Sox5 and Sox6 are essential for controlling cell cycle exit in neural progenitors (Martinez-Morales et al., 2010) and for interneuron subtypes specification (Quiroga et al., 2015) in the developing spinal cord. Sox5 and Sox6 and are also expressed in neural stem cells and progenitors of adult brain neurogenic niches (our unpublished results). We are currently testing the hypothesis that Sox5 and Sox6 could control the activation, proliferation and/or self-renewal of NSCs in adult hippocampal neurogenesis promoting similar gene programs that induce during embryonic neurogenesis but also other specific, that could shed light on the particularities of the very restricted process (both in the number and in the cell subtypes generated) of adult neurogenesis. For that purpose we are using inducible targeted deletions: Sox5fl+/fl+ and Sox6fl+/fl+ mice crossed to a transgenic Sox2-cre-ERT2 line inducible by tamoxifen.
The project offered for the TFM will involve the analysis of the brain slices of the inducible mutant mice by fluorescence inmunohystochemistry using especific cell markers and the quantification on confocal images. Additionally, it will also involve in vitro analysis using cell adherent cultures and neurospheres obtained from the mutant mice hippocampus.