, 2005) These early patterning functions of Shh and

othe

, 2005). These early patterning functions of Shh and

other Hedgehog family members are mediated by the transmembrane receptor Patched (Ptch) and the seven-pass transmembrane protein Smoothened (Smo) which signals through a “canonical” signaling pathway involving transcriptional regulators of the Gli family (Lum and Beachy, 2004). Surprisingly, Shh was more recently involved in axon guidance independently of its patterning functions (Charron et al., 2003). This axon guidance function is mediated by activation of a “noncanonical” receptor called Brother Of CDO (Boc), a Robo-related Ig/fibronectin superfamily member that can bind with high affinity to Shh and other Hedgehog family members (Okada et al., 2006). Callosal projections represents a great illustration of the precise, layer-specific, synaptic organization of cortical circuits (Fame et al., 2011; Figures 1A and

1B): neurons from the superficial layers 2/3 have their axon projecting medially Docetaxel supplier through the corpus callosum to establish topographically organized connections with the equivalent areal position in the controlateral hemisphere. These projections are layer selleck specific, making glutamatergic excitatory synaptic connections mainly with layer 5 pyramidal neurons projecting subcortically and with other layer 2/3 pyramidal neurons (Figures 1A and 1B). The axons of layer 2/3 callosally projecting neurons also make excitatory synaptic contacts with layer 5 neurons ipsilaterally (Figures 1A and 1B). The molecular mechanisms underlying mafosfamide the establishment of these layer-specific patterns of synaptic connectivity are largely unknown. In the present study, Harwell et al. (2012) observed that Shh expression persists in the postnatal mouse neocortex long after its “patterning” function during embryonic development is over. Interestingly, Shh expression is largely restricted to pyramidal neurons in layer 5. Using combination of retrograde

axon tracing, layer-specific marker expression and lineage tracing using a Shh-Cre;Rosa26-LoxP-STOP-LoxP-YFP reporter mouse line, the authors identified that Shh expression is largely restricted to CTIP2-positive, corticospinal-projecting neurons of layer 5b. Conditional deletion of Shh from most pyramidal glutamatergic neocortical neurons by crossing conditional Shh knockout mice with the dorsal telencephalon-specific driver Emx1Cre (Gorski et al., 2002) has no major consequence on brain patterning, most likely because it does not disrupt Shh expression at the ventral midline where it plays its patterning function in the embryonic telencephalon. Conditional deletion of Shh seemed to have little or no effect on the number, survival, and axon guidance of corticospinal projecting neurons. However, the authors observed layer-specific dendritic defects: in Shh cKO brains, neurons displayed reduced dendritic arborization and a reduced spine density specifically in layer 5, whereas neurons from superficial layers 2/3 appeared unaffected.

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