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The Journal of Neuroscience, April 11, 2007, 27(15):4132-4145; doi:10.1523/JNEUROSCI.0111-07.2007

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Development/Plasticity/Repair
Human Cortical Neurons Originate from Radial Glia and Neuron-Restricted Progenitors

Zhicheng Mo,¹ Anna R. Moore,¹ Radmila Filipovic,¹ Yasuhiro Ogawa,² Ikenaka Kazuhiro,² Srdjan D. Antic,¹ and Nada Zecevic¹

¹Department of Neuroscience, University of Connecticut Health Center, Farmington, Connecticut 06030, and ²Division of Neurobiology and Bioinformatics, National Institute for Physiological Sciences, Myodaiji, Okazaki, Aichi 444-8787, Japan

Correspondence should be addressed to Dr. Nada Zecevic, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030-3401. Email: nzecevic{at}neuron.uchc.edu

Understanding the molecular and physiological determinants of cortical neuronal progenitor cells is essential for understanding the development of the human brain in health and in disease. We used surface marker fucose N-acetyl lactosamine (LeX) (also known as CD15) to isolate progenitor cells from the cortical ventricular/subventricular zone of human fetal brain at the second trimester of gestation and to study their progeny in vitro. LeX⁺ cells had typical bipolar morphology, radial orientation, and antigen profiles, characterizing them as a subtype of radial glia (RG) cells. Four complementary experimental techniques (clonal analysis, immunofluorescence, transfection experiments, and patch-clamp recordings) indicated that this subtype of RG generates mainly astrocytes but also a small number of cortical neurons. The neurogenic capabilities of RGs were both region and stage dependent. Present results provide the first direct evidence that RGs in the human cerebral cortex serve as neuronal progenitors. Simultaneously, another progenitor subtype was identified as proliferating cells labeled with neuronal (ß-III-tubulin and doublecortin) but not RG markers [GFAP, vimentin, and BLBP (brain lipid-binding protein)]. Proliferative and antigenic characteristics of these cells suggested their neuron-restricted progenitor status. In summary, our in vitro study suggests that diverse populations of cortical progenitor cells, including multipotent RGs and neuron-restricted progenitors, contribute differentially to cortical neurogenesis at the second trimester of gestation in human cerebral cortex.

Key words: cerebral cortex development; primates; human fetal cell cultures; LeX immunocytochemistry; transfection; patch-clamp recording

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Received Aug. 23, 2006; revised March 8, 2007; accepted March 9, 2007.

Correspondence should be addressed to Dr. Nada Zecevic, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030-3401. Email: nzecevic{at}neuron.uchc.edu

This article has been cited by other articles:

				A. R. Moore, R. Filipovic, Z. Mo, M. N. Rasband, N. Zecevic, and S. D. Antic Electrical Excitability of Early Neurons in the Human Cerebral Cortex during the Second Trimester of Gestation Cereb Cortex, August 1, 2009; 19(8): 1795 - 1805. [Abstract] [Full Text] [PDF]

				B. M. Howard, Zhicheng Mo, R. Filipovic, A. R. Moore, S. D. Antic, and N. Zecevic Radial Glia Cells in the Developing Human Brain Neuroscientist, October 1, 2008; 14(5): 459 - 473. [Abstract] [PDF]

				N. Bayatti, J. A. Moss, L. Sun, P. Ambrose, J. F. H. Ward, S. Lindsay, and G. J. Clowry A Molecular Neuroanatomical Study of the Developing Human Neocortex from 8 to 17 Postconceptional Weeks Revealing the Early Differentiation of the Subplate and Subventricular Zone Cereb Cortex, July 1, 2008; 18(7): 1536 - 1548. [Abstract] [Full Text] [PDF]

				Z. Mo and N. Zecevic Is Pax6 Critical for Neurogenesis in the Human Fetal Brain? Cereb Cortex, June 1, 2008; 18(6): 1455 - 1465. [Abstract] [Full Text] [PDF]

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