Sonic hedgehog signaling confers ventral telencephalic progenitors with distinct cortical interneuron fates.
Interneurons in the cerebral cortex regulate cortical functions through the actions of distinct subgroups that express parvalbumin, somatostatin, or calretinin. The genesis of the first two subgroups requires the expression of NKX2.1, which is maintained by SHH signaling during neurogenesis. In this paper, we report that mosaic elimination in the medial ganglionic eminence (MGE) of Smo, a key effector of SHH signaling, reveals that MGE progenitors retain a remarkable degree of plasticity during the neurogenic period. SHH signaling prevents the upregulation of GSX2 and conversion of some MGE progenitors to a caudal ganglionic eminence-like, bipolar calretinin-expressing cell fate that is promoted by GSX2. In addition, a higher level of SHH signaling promotes the generation of the somatostatin-expressing interneuron at the expense of parvalbumin-expressing subgroup. These results indicate that cortical interneuron diversity, a major determinant of cortical function, is critically influenced by differential levels of SHH signaling within the ventral telencephalon.
Weill Cornell Medical College, 1300 York Avenue New York, NY 10065, USA.
Qing
Q
Xu
Lihua
L
Guo
Holly
H
Moore
Ronald R
RR
Waclaw
Kenneth
K
Campbell
Stewart A
SA
Anderson
D000818:Animals; D030801:Animals, Genetically Modified; D064032:Calbindin 2; D002540:Cerebral Cortex / Q000166:cytology*; D004622:Embryo, Mammalian; D053595:Embryonic Stem Cells / Q000502:physiology*; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007395:Interneurons / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010320:Parvalbumins / Q000378:metabolism; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013004:Somatostatin / Q000378:metabolism; D013687:Telencephalon / Q000166:cytology*; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000097607:Homeobox Protein SIX3
D064032:Calbindin 2; D005136:Eye Proteins; D049452:Green Fluorescent Proteins; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D010320:Parvalbumins; D064030:S100 Calcium Binding Protein G; D013004:Somatostatin; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; D000097607:Homeobox Protein SIX3; C576511:Calb2 protein, mouse; C109498:Gsh2 protein, mouse; C000614414:Nkx2-1 protein, mouse