Defects in neuronal differentiation and axonal connectivity in mice mutant in the Sox2 transcription factor gene: in vitro and in vivo studies

Sox2 is an important transcription factor expressed in the central nervous system from the beginning of its development. We generated Sox2 mutant mice carrying a “knockdown” mutation together with a null mutation, which express 20-30% of the normal amount of Sox2. These mice show brain abnormalities including decreased cortical size, defects in neurogenesis and cell death in thalamus (Ferri et al., 2004). We also generated Sox2 conditional mutant mice, in wich the Sox2 locus is flanked by loxP sites, and it can be ablated by driven expression of a Cre recombianse. These mice show brain abnormalities including e decreased size of posterior cortex. (Favaro et al.). Around the time of neurogenesis, neocortex and dorsal thalamus start to become connected through reciprocal axonal projections. The complete process in mice occurs between E13 and E18. I hypothesize that in Sox2 mutants the thalamocortical and corticothalamic connections may be affected. I studied if the cortical neurons are able to grow and form correct connections in Sox2 hypomorphic mice and in conditional Sox2 mutant mice, in which Sox2 in completely ablated in the central nervous system from E12,5 via a Nestin Cre transgene, or is deleted from specific regions of the brain via Cre driven by genes specifically expressed in cortex or thalamus