Hedgehog signaling is involved in development of the neocortex

Abstract

Sonic hedgehog (Shh) function is essential for patterning and cell fate specification, particularly in ventral regions of the central nervous system. It is also a crucial mitogen for cerebellar granule neuron precursors and is important in maintenance of the stem cell niche in the postnatal telencephalon. Although it has been reported that Shh is expressed in the developing dorsal telencephalon, functions of Shh in this region are unclear, and detailed characterization of Shh mRNA transcripts in situ has not been demonstrated. To clarify the roles of Shh signaling in dorsal pallium (neocortex primordium) development, we have knocked out the Shh and Smo genes specifically in the early developing dorsal telencephalon by using Emx1 cre mice. The mutants showed a smaller dorsal telencephalon at E18.5, which was caused by cell cycle kinetics defects of the neural progenitor/stem cells. The cell cycle length of the progenitor/stem cells was prolonged, and the number of cycle-exiting cells and neurogenesis were decreased. Birth-date analysis revealed abnormal positioning of neurons in the mutants. The characteristics of the subventricular zone, ventricular zone and subplate cells were also affected. Weak immunoreactivity of Shh was detected in the dorsal telencephalon of wild types. Reduced Shh immunoreactivity in mutant dorsal telencephalons supports the above phenotypes. Our data indicate that Shh signaling plays an important role in development of the neocortex.

Role of NeuroepithelialSonic hedgehogin Hypothalamic Patterning

“…The Foxb1-expressing area of MAM neuroepithelium was measured on photographs with the help of CellF 2.6 software (Olympus Soft Imaging Solutions). (Dassule et al, 2000;Lewis et al, 2001;Machold et al, 2003;Komada et al, 2008). On Cre-mediated recombination, the floxed Shh loses exon 2 (Dassule et al, 2000;Lewis et al, 2001) Roelink et al, 1995).…”

Expression analysis of Sulf1 in the chick forebrain at early and late stages of development

“…Although no evident relationship between this pattern of expression and Shh signaling can be proposed, we do not exclude a possible function for Sulf1 in modulating Shh signaling in these cells. Indeed, Shh has recently been identified as a trophic signal for different neuronal populations in the telencephalon and cerebellum (Komada et al, 2008;revised in Vaillant and Monard, 2009). …”

Cils et migrations neuronales

“…Shh est exprimé dans les voies de migration tangentielle du cortex au stade embryonnaire, lorsque les cellules de l'EGM colonisent le cortex [19] (Figure 2D). Nous avons donc recherché si la migration des neurones GABAergiques est influencée par Shh, et si l'ablation géné-tique du cil primaire perturbe la réponse des neurones GABAergiques à Shh.…”