Multiple Origins of Human Neocortical Interneurons Are Supported by Distinct Expression of Transcription Factors (original) (raw)

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1Department of Neuroscience, University of Connecticut Health Center, Farmington, CT 06030, USA

2Center for Molecular Neurobiology Hamburg, Falkenried 94, 20251, Hamburg, Germany

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1Department of Neuroscience, University of Connecticut Health Center, Farmington, CT 06030, USA

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1Department of Neuroscience, University of Connecticut Health Center, Farmington, CT 06030, USA

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Published:

07 December 2010

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Igor Jakovcevski, Nicole Mayer, Nada Zecevic, Multiple Origins of Human Neocortical Interneurons Are Supported by Distinct Expression of Transcription Factors, Cerebral Cortex, Volume 21, Issue 8, August 2011, Pages 1771–1782, https://doi.org/10.1093/cercor/bhq245
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Abstract

Cortical γ-aminobutyric acid (GABA)ergic interneurons in rodents originate mainly in ventrally positioned ganglionic eminences (GEs), but their origin in primates is still debated. We studied human fetal forebrains during the first half of gestation (5–23 gestational weeks, gw) for the expression of ventral transcription factors, Nkx2.1, Dlx1,2, Lhx6, and Mash1, important for development of neocortical interneurons. In embryonic (5–8 gw) human forebrain, these factors were expressed in the GE but also dorsally in the neocortical ventricular/subventricular zones (VZ/SVZ). Furthermore, their expression was retained in cells of all fetal cortical layers up to midgestation (20 gw). Nkx2.1 continued to be expressed not only in the GE but also in a subpopulation of neocortical interneurons. Moreover, proliferation marker Ki67 revealed that calretinin+, Mash1+, and Nkx2.1+ cells proliferate in the neocortical VZ/SVZ at midgestation. At least some of the Mash1+ progenitors in the neocortical SVZ could be colabeled with GABA, whereas others were oligodendrocyte progenitors, indicating a link between the 2 lineages. Taken together, these results suggest the existence of several categories of dorsal interneuronal progenitors in the human neocortical VZ/SVZ, in addition to ventrally derived cortical interneurons described in rodents. These human-specific developmental events may underlie human brain's higher complexity and capacity to process information.

© The Author 2010. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Topic:

• gamma-aminobutyric acid
• fetus
• ganglia
• interneurons
• oligodendroglia
• primates
• prosencephalon
• rodentia
• brain
• transcription factor
• calretinin
• ascl1 protein, human
• lhx6 gene

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