Maturation of cortical circuits requires Semaphorin 7A

Abstract

Abnormal cortical circuits underlie some cognitive and psychiatric disorders, yet the molecular signals that generate normal cortical networks remain poorly understood. Semaphorin 7A (Sema7A) is an atypical member of the semaphorin family that is GPI-linked, expressed principally postnatally, and enriched in sensory cortex. Significantly, SEMA7A is deleted in individuals with 15q24 microdeletion syndrome, characterized by developmental delay, autism, and sensory perceptual deficits. We studied the role that Sema7A plays in establishing functional cortical circuitry in mouse somatosensory barrel cortex. We found that Sema7A is expressed in spiny stellate cells and GABAergic interneurons and that its absence disrupts barrel cytoarchitecture, reduces asymmetrical orientation of spiny stellate cell dendrites, and functionally impairs thalamocortically evoked synaptic responses, with reduced feed-forward GABAergic inhibition. These data identify Sema7A as a regulator of thalamocortical and local circuit development in layer 4 and provide a molecular handle that can be used to explore the coordinated generation of excitatory and inhibitory cortical circuits.E/I balance | critical period | EPSPs | IPSPs | thalamocortical

GABAergic cell loss in mice lacking autism-associated geneSema6A

“…While most studies have focused on the importance of semaphorins in the control of neuronal migration and axon guidance during brain development, recent studies have reported the role of semaphorins in the maturation of cortical circuits [55,56]. Indeed failure in GABAergic circuitry formation was described in the Sema7A knockout mice, however the GABAergic cell loss was only reported in layer 4 of the barrel cortex [55] compared to our results showing that all the cortical layers are affected in the Sema6A mutation. More recently, Greg Barnes' group published an informative study on interneuronspecific knockout mouse of Sema3F [56].…”

“…Such defects in CC formation were also reported in Sema3A knockout mice [33,53] and provide more evidence for a role of semaphorin members in ASD as 1/3 of individuals with autism have an abnormal CC [54]. While most studies have focused on the importance of semaphorins in the control of neuronal migration and axon guidance during brain development, recent studies have reported the role of semaphorins in the maturation of cortical circuits [55,56]. Indeed failure in GABAergic circuitry formation was described in the Sema7A knockout mice, however the GABAergic cell loss was only reported in layer 4 of the barrel cortex [55] compared to our results showing that all the cortical layers are affected in the Sema6A mutation.…”

Shaping the Reproductive System: Role of Semaphorins in Gonadotropin-Releasing Hormone Development and Function

“…The pleiotropic nature of semaphorins is particularly evident for Sema7A, whose roles in immune function [74] and cancer biology [75,76,77] have been extensively studied. In addition, a few reports have addressed its role in neuronal development [78,79,80,81,82]. A study performed in our laboratory has revealed a role for Sema7A and its two receptors, PlexinC1 and β 1 -integrin, in the regulation of GnRH cell motility [24].…”

Rewiring the taste system

“…Our expression profiling studies (Fig. 1b, 4a-b) singled-out Sema7A, a membrane-bound member of the semaphorin family 25,26 , as highly selective for sweet cells. To investigate the role of Sema7A in guiding sweet TRC-ganglion connectivity, we engineered animals that mis-express Sema7A in bitter TRCs (Extended Data Fig.…”