RRC ID 47432
著者 Poon CL, Mitchell KA, Kondo S, Cheng LY, Harvey KF.
タイトル The Hippo Pathway Regulates Neuroblasts and Brain Size in Drosophila melanogaster.
ジャーナル Curr Biol
Abstract A key question in developmental neurobiology is how neural stem cells regulate their proliferative potential and cellular diversity and thus specify the overall size of the brain. Drosophila melanogaster neural stem cells (neuroblasts) are known to regulate their ability to self-renew by asymmetric cell division and produce different types of neurons and glia through sequential expression of temporal transcription factors [1]. Here, we show that the conserved Hippo pathway, a key regulator of epithelial organ size [2-4], restricts neuroblast proliferative potential and neuronal cell number to regulate brain size. The inhibition of Hippo pathway activity via depletion of the core kinases Tao-1, Hippo, or Warts regulates several key characteristics of neuroblasts during postembryonic neurogenesis. The Hippo pathway is required to maintain timely entry and exit from neurogenesis by regulating both neuroblast reactivation from quiescence and the time at which neuroblasts undergo terminal differentiation. Further, it restricts neuroblast cell-cycle speed, specifies cell size, and alters the proportion of neuron types generated during postembryonic neurogenesis. Collectively, deregulation of Hippo signaling in neuroblasts causes a substantial increase in overall brain size. We show that these effects are mediated via the key downstream transcription co-activator Yorkie and that, indeed, Yorkie overexpression in neuroblasts is sufficient to cause brain overgrowth. These studies reveal a novel mechanism that controls stem cell proliferative potential during postembryonic neurogenesis to regulate brain size.
巻・号 26(8)
ページ 1034-42
公開日 2016-4-25
DOI 10.1016/j.cub.2016.02.009
PII S0960-9822(16)30061-6
PMID 26996505
MeSH Animals Brain / growth & development Brain / metabolism Cell Proliferation Drosophila Proteins / genetics Drosophila Proteins / metabolism Drosophila melanogaster / genetics Drosophila melanogaster / growth & development* Drosophila melanogaster / metabolism* Gene Expression Regulation, Developmental Intracellular Signaling Peptides and Proteins / genetics Intracellular Signaling Peptides and Proteins / metabolism Neural Stem Cells / cytology Neural Stem Cells / metabolism* Neurogenesis* Nuclear Proteins / genetics Nuclear Proteins / metabolism Organ Size Protein Kinases / genetics Protein Kinases / metabolism Protein Serine-Threonine Kinases / genetics Protein Serine-Threonine Kinases / metabolism Signal Transduction* Trans-Activators / genetics Trans-Activators / metabolism YAP-Signaling Proteins
IF 9.601
引用数 41
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY
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