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Cereb Cortex. 2018 Jun 1;28(6):1946-1958. doi: 10.1093/cercor/bhx101.

Secretagogin is Expressed by Developing Neocortical GABAergic Neurons in Humans but not Mice and Increases Neurite Arbor Size and Complexity.

Author information

1
Department of Neurological Surgery, University of California, San Francisco, USA.
2
The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, USA.
3
Neurona Therapeutics, South San Francisco, CA, USA.
4
Department of Psychiatry, University of California, San Francisco, USA.
5
EntroGen, Woodland Hills, CA, USA.
6
Center for Integrative Neuroscience, University of California, San Francisco, USA.
7
Department of Neurology, University of California, San Francisco, USA.
8
Howard Hughes Medical Institute and Department of Biology, Stanford University, Stanford, CA, USA.
9
Department of Otolaryngology-Head and Neck Surgery, University of California, San Francisco, USA.

Abstract

The neocortex of primates, including humans, contains more abundant and diverse inhibitory neurons compared with rodents, but the molecular foundations of these observations are unknown. Through integrative gene coexpression analysis, we determined a consensus transcriptional profile of GABAergic neurons in mid-gestation human neocortex. By comparing this profile to genes expressed in GABAergic neurons purified from neonatal mouse neocortex, we identified conserved and distinct aspects of gene expression in these cells between the species. We show here that the calcium-binding protein secretagogin (SCGN) is robustly expressed by neocortical GABAergic neurons derived from caudal ganglionic eminences (CGE) and lateral ganglionic eminences during human but not mouse brain development. Through electrophysiological and morphometric analyses, we examined the effects of SCGN expression on GABAergic neuron function and form. Forced expression of SCGN in CGE-derived mouse GABAergic neurons significantly increased total neurite length and arbor complexity following transplantation into mouse neocortex, revealing a molecular pathway that contributes to morphological differences in these cells between rodents and primates.

PMID:
28449024
PMCID:
PMC6019052
[Available on 2019-06-01]
DOI:
10.1093/cercor/bhx101
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