title: Hedgehog signaling promotes basal progenitor expansion and the growth and folding of the neocortex.
abstract: The unique mental abilities of humans are rooted in the immensely expanded and folded neocortex, which reflects the expansion of neural progenitors, especially basal progenitors including basal radial glia (bRGs) and intermediate progenitor cells (IPCs). We found that constitutively active Sonic hedgehog (Shh) signaling expanded bRGs and IPCs and induced folding in the otherwise smooth mouse neocortex, whereas the loss of Shh signaling decreased the number of bRGs and IPCs and the size of the neocortex. SHH signaling was strongly active in the human fetal neocortex but Shh signaling was not strongly active in the mouse embryonic neocortex, and blocking SHH signaling in human cerebral organoids decreased the number of bRGs. Mechanistically, Shh signaling increased the initial generation and self-renewal of bRGs and IPC proliferation in mice and the initial generation of bRGs in human cerebral organoids. Thus, robust SHH signaling in the human fetal neocortex may contribute to bRG and IPC expansion and neocortical growth and folding.
authors.affiliation: Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.|Division of Brain Tumor Research, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.|Division of Brain Tumor Research, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: Shirui
authors.initials: S
authors.lastname: Hou
authors.affiliation: Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.|Division of Brain Tumor Research, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: Young-Goo
authors.identifier: 0000-0002-4008-294X
authors.initials: YG
authors.lastname: Han
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D053823:Hedgehog Proteins / Q000235:genetics; D008822:Mice, Transgenic; D019579:Neocortex / Q000378:metabolism*; D058953:Neural Stem Cells / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D053823:Hedgehog Proteins