Shinjini Basu, Lena Mautner, Kae Whiting, Kerstin Hasenpusch-Theil, Malgorzata Borkowska, Thomas Theil
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引用次数: 0
Abstract
The cerebral cortex is critical for advanced cognitive functions and relies on a vast network of neurons to carry out its highly intricate neural tasks. Generating cortical neurons in accurate numbers hinges on cell signaling orchestrated by primary cilia to coordinate the proliferation and differentiation of cortical stem cells. While recent research has shed light on multiple ciliary roles in corticogenesis, specific mechanisms downstream of cilia signaling remain largely unexplored. We previously showed that an excess of early-born cortical neurons in mice mutant for the ciliary gene Inpp5e was rescued by re-introducing Gli3 repressor. By comparing expression profiles between Inpp5e and Gli3 mutants, we here identified novel Gli3 target genes. This approach highlighted the transcription factor gene Sall3 and Pappalysin1 (Pappa), a metalloproteinase involved in IGF signaling, as upregulated genes in both mutants. Further examination revealed that Gli3 directly binds to Sall3 and Pappa enhancers and suppresses their activity in the dorsal telencephalon. Collectively, our analyses provide important mechanistic insights into how primary cilia govern the behavior of neural stem cells, ultimately ensuring the production of adequate numbers of neurons during corticogenesis.
期刊介绍:
Cerebral Cortex publishes papers on the development, organization, plasticity, and function of the cerebral cortex, including the hippocampus. Studies with clear relevance to the cerebral cortex, such as the thalamocortical relationship or cortico-subcortical interactions, are also included.
The journal is multidisciplinary and covers the large variety of modern neurobiological and neuropsychological techniques, including anatomy, biochemistry, molecular neurobiology, electrophysiology, behavior, artificial intelligence, and theoretical modeling. In addition to research articles, special features such as brief reviews, book reviews, and commentaries are included.