title: The Role of Sonic Hedgehog in the Specification of Human Cortical Progenitors In Vitro.
abstract: Impaired sonic hedgehog (Shh) signaling is involved in the pathology of cortical formation found in neuropsychiatric disorders. However, its role in the specification of human cortical progenitors is not known. Here, we report that Shh is expressed in the human developing cortex at mid-gestation by radial glia cells (RGCs) and cortical neurons. We used RGC cultures, established from the dorsal (cortical) telencephalon of human brain at mid-gestation to study the effect of Shh signaling. Cortical RGCs in vitro maintained their regional characteristics, expressed components of Shh signaling, and differentiated into Nkx2.1, Lhx6, and calretinin-positive (CalR(+)) cells, potential cortical interneuron progenitors. Treatment with exogenous Shh increased the pool of Nkx2.1(+) progenitors, decreased Lhx6 expression, and suppressed the generation of CalR(+) cells. The blockade of endogenous Shh signaling increased the number of CalR(+) cells, but did not affect Nkx2.1 expression, implying the existence of parallel Shh-independent pathways for cortical Nkx2.1 regulation. These results support the idea that, during human brain development, Shh plays an important role in the specification of cortical progenitors. Since direct functional studies in humans are limited, the in vitro system that we established here could be of great interest for modeling the development of human cortical progenitors.
authors.affiliation: Department of Neuroscience, University of Connecticut Health Center, Farmington, CT 06030, USA Institute of Medical and Clinical Biochemistry, School of Medicine, University of Belgrade, 11000 Belgrade, Serbia.
authors.forename: Nevena V
authors.initials: NV
authors.lastname: Radonjić
authors.affiliation: Department of Neuroscience, University of Connecticut Health Center, Farmington, CT 06030, USA.
authors.forename: Fani
authors.initials: F
authors.lastname: Memi
authors.affiliation: Department of Neuroscience, University of Connecticut Health Center, Farmington, CT 06030, USA.
authors.forename: Juan Alberto
authors.initials: JA
authors.lastname: Ortega
authors.affiliation: Department of Neuroscience, University of Connecticut Health Center, Farmington, CT 06030, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Glidden
authors.affiliation: Department of Neuroscience, University of Connecticut Health Center, Farmington, CT 06030, USA.
authors.forename: Haiying
authors.initials: H
authors.lastname: Zhan
authors.affiliation: Department of Neuroscience, University of Connecticut Health Center, Farmington, CT 06030, USA.
authors.forename: Nada
authors.initials: N
authors.lastname: Zecevic
mesh_terms: D000293:Adolescent; D000328:Adult; D002118:Calcium / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage / Q000502:physiology*; D002540:Cerebral Cortex / Q000166:cytology; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D007395:Interneurons / Q000166:cytology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D013687:Telencephalon / Q000166:cytology*; D055815:Young Adult
chemical_list: D053823:Hedgehog Proteins; D009419:Nerve Tissue Proteins; C509239:SHH protein, human; D002118:Calcium
keywords: Lhx6; Nkx2.1; calretinin; cortical interneurons; development of human cerebral cortex; radial glia cultures