title: Extended Production of Cortical Interneurons into the Third Trimester of Human Gestation.
abstract: 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.
authors.affiliation: Department of Pediatrics.
authors.forename: Arslan
authors.initials: A
authors.lastname: Arshad
authors.affiliation: 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.
authors.forename: Linnea R
authors.initials: LR
authors.lastname: Vose
authors.affiliation: 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.
authors.forename: Govindaiah
authors.initials: G
authors.lastname: Vinukonda
authors.affiliation: Department of Pediatrics.
authors.forename: Furong
authors.initials: F
authors.lastname: Hu
authors.affiliation: Institute for Protein Research Osaka University Yamadaoka, Osaka, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Yoshikawa
authors.affiliation: Department of Geriatric Medicine, Reynolds Oklahoma Center of Aging, University of Oklahoma Health Science Center, Oklahoma City, OK, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Csiszar
authors.affiliation: 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.
authors.forename: Joshua C
authors.initials: JC
authors.lastname: Brumberg
authors.affiliation: 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.
authors.forename: Praveen
authors.initials: P
authors.lastname: Ballabh
mesh_terms: D001921:Brain / Q000196:embryology* / Q000378:metabolism / Q000502:physiology*; D002452:Cell Count; D002540:Cerebral Cortex / Q000196:embryology / Q000378:metabolism / Q000502:physiology; D005260:Female; D047109:Fetal Development; D059330:GABAergic Neurons / Q000378:metabolism / Q000502:physiology*; D005865:Gestational Age; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D007395:Interneurons / Q000378:metabolism / Q000502:physiology*; D020547:Lateral Ventricles / Q000196:embryology / Q000378:metabolism / Q000502:physiology; D008297:Male; D008473:Median Eminence / Q000196:embryology / Q000502:physiology; D058953:Neural Stem Cells / Q000378:metabolism / Q000502:physiology*; D055495:Neurogenesis; D009687:Nuclear Proteins / Q000378:metabolism; D011247:Pregnancy; D011263:Pregnancy Trimester, Third; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000378:metabolism
chemical_list: C088334:Distal-less homeobox proteins; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors
keywords: Dlx2; GABAergic; Nkx2.1; Sox2; ganglionic eminence; interneuron; subventricular zone