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Cereb Cortex. 2016 May;26(5):2242-2256. doi: 10.1093/cercor/bhv074. Epub 2015 Apr 16.

Extended Production of Cortical Interneurons into the Third Trimester of Human Gestation.

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Department of Pediatrics.
Department of Cell Biology and Anatomy, Regional Neonatal Center, Maria Fareri Children's Hospital at Westchester Medical Center-New York Medical College, Valhalla, NY, USA.
Institute for Protein Research Osaka University Yamadaoka, Osaka, Japan.
Department of Geriatric Medicine, Reynolds Oklahoma Center of Aging, University of Oklahoma Health Science Center, Oklahoma City, OK, USA.
Psychology and Biology PhD Programs, The Graduate Center, City University of New York, New York, NY, USA.
Department of Psychology, Queens College, City University of New York, Flushing, NY, USA.


In humans, the developmental origins of interneurons in the third trimester of pregnancy and the timing of completion of interneuron neurogenesis have remained unknown. Here, we show that the total and cycling Nkx2.1(+)and Dlx2(+)interneuron progenitors as well as Sox2(+)precursor cells were higher in density in the medial ganglionic eminence (MGE) compared with the lateral ganglionic eminence and cortical ventricular/subventricular zone (VZ/SVZ) of 16-35 gw subjects. The proliferation of these progenitors reduced as a function of gestational age, almost terminating by 35 gw. Proliferating Dlx2(+)cells were higher in density in the caudal ganglionic eminence (CGE) compared with the MGE, and persisted beyond 35 gw. Consistent with these findings, Sox2, Nkx2.1, Dlx2, and Mash1 protein levels were higher in the ganglionic eminences relative to the cortical VZ/SVZ. The density of gamma-aminobutyric acid-positive (GABA(+)) interneurons was higher in the cortical VZ/SVZ relative to MGE, but Nkx2.1 or Dlx2-expressing GABA(+)cells were more dense in the MGE compared with the cortical VZ/SVZ. The data suggest that the MGE and CGE are the primary source of cortical interneurons. Moreover, their generation continues nearly to the end of pregnancy, which may predispose premature infants to neurobehavioral disorders.


Dlx2; GABAergic; Nkx2.1; Sox2; ganglionic eminence; interneuron; subventricular zone

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