Abstract
The formation of a laminar structure such as the mammalian neocortex relies on the coordinated migration of different subtypes of excitatory pyramidal neurons in specific layers. Cyclin-dependent kinase 5 (Cdk5) is a master regulator of pyramidal neuron migration. Recently, we have shown that Cdk5 binds to the serotonin 6 receptor (5-HT6R), a G protein-coupled receptor (GPCR). Here, we investigated the role of 5-HT6R in the positioning and migration of pyramidal neurons during mouse corticogenesis. We report that constitutive expression of 5-HT6R controls pyramidal neuron migration through an agonist-independent mechanism that requires Cdk5 activity. These data provide the first in vivo evidence of a role for constitutive activity at a GPCR in neocortical radial migration.
Highlights
Cortical circuit formation relies on the migration of pyramidal neurons (PNs) into specific layers (Rakic et al, 2007; Marin et al, 2010) and cell-extrinsic factors such as neurotransmitters have been shown to regulate their migration (Heng et al, 2007)
Taken together, our results demonstrate that the 5-HT6R controls migration of PNs through an agonist-independent, Cyclin-dependent kinase 5 (Cdk5)-dependent, mechanism
It should be mentioned that an excess of serotonin, as well as pharmacological manipulation of 5-HT6R, have been shown to affect neuronal migration in cortical slices (Riccio et al, 2009, 2011), suggesting a role for ligand-induced activation of the 5-HT6R in modulating neuronal migration, possibly in conditions where there is a pathological excess of serotonin
Summary
Cortical circuit formation relies on the migration of pyramidal neurons (PNs) into specific layers (Rakic et al, 2007; Marin et al, 2010) and cell-extrinsic factors such as neurotransmitters have been shown to regulate their migration (Heng et al, 2007). Distinct steps are involved in the migration of PNs before they reach their final position in the cortical plate (CP) (Heng et al, 2007; Rakic et al, 2007; Marin et al, 2010).
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