Abstract:
:Neurofibromatosis type 1 (NF1) is a common neurodevelopmental disorder caused by impaired function of the neurofibromin RAS regulator. Using a combination of Nf1 genetically engineered mice and pharmacological/genetic inhibition approaches, we report that neurofibromin differentially controls neural stem cell (NSC) proliferation and multilineage differentiation through the selective use of the PI3K/AKT and RAF/MEK pathways. While PI3K/AKT governs neurofibromin-regulated NSC proliferation, multilineage differentiation is MEK-dependent. Moreover, whereas MEK-regulated multilineage differentiation requires Smad3-induced Jagged-1 expression and Notch activation, MEK/Smad3-regulated Hes1 induction is only responsible for astrocyte and neuronal differentiation. Collectively, these findings establish distinct roles for the RAS effector pathways in regulating brain NSC function.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Chen YH,Gianino SM,Gutmann DHdoi
10.1101/gad.261677.115subject
Has Abstractpub_date
2015-08-15 00:00:00pages
1677-82issue
16eissn
0890-9369issn
1549-5477pii
gad.261677.115journal_volume
29pub_type
杂志文章abstract::Bistability in developmental pathways refers to the generation of binary outputs from graded or noisy inputs. Signaling thresholds are critical for bistability. Specification of the left/right (LR) axis in vertebrate embryos involves bistable expression of transforming growth factor beta (TGFbeta) member NODAL in the ...
journal_title:Genes & development
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journal_title:Genes & development
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abstract::Nitric oxide (NO) is an important second messenger involved in numerous biological processes, but how it regulates gene expression is not well understood. In this issue of Genes & Development, Cáceres and colleagues (pp. 1476-1485) report a critical requirement of NO as a direct regulator of gene expression through it...
journal_title:Genes & development
pub_type: 评论,杂志文章
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journal_title:Genes & development
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journal_title:Genes & development
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journal_title:Genes & development
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journal_title:Genes & development
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journal_title:Genes & development
pub_type: 杂志文章
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journal_title:Genes & development
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.9.22.2747
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abstract::Long-range migrating progenitor cells generate hypaxial muscle, for instance the muscle of the limbs, hypoglossal cord, and diaphragm. We show here that migrating muscle progenitors express the chemokine receptor CXCR4. The corresponding ligand, SDF1, is expressed in limb and branchial arch mesenchyme; i.e., along the...
journal_title:Genes & development
pub_type: 杂志文章
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abstract::The Hox gene products are transcription factors involved in specifying regional identity along the anteroposterior body axis. In the mouse, several single mutants for Hox genes show variably penetrant, partial homeotic transformations of vertebrae at their anterior limits of expression, suggesting that compound Hox mu...
journal_title:Genes & development
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journal_title:Genes & development
pub_type: 评论,杂志文章
doi:10.1101/gad.223172.113
更新日期:2013-06-15 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
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journal_title:Genes & development
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journal_title:Genes & development
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更新日期:2008-06-01 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.8.11.1300
更新日期:1994-06-01 00:00:00
abstract::In the July 15, 2010, issue of Genes & Development, Yoon and colleagues (pp. 1507-1518) report that, in a siRNA knockdown survey of 6363 genes in mouse C2C12 cells, they discovered 150 genes that regulated mitochondrial biogenesis and bioenergetics. Many of these genes have been studied previously for their importance...
journal_title:Genes & development
pub_type: 评论,杂志文章
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更新日期:2010-08-01 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1856210
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journal_title:Genes & development
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journal_title:Genes & development
pub_type: 评论,杂志文章,评审
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journal_title:Genes & development
pub_type: 杂志文章
doi:
更新日期:2000-02-01 00:00:00