Engineering of dominant active basic helix-loop-helix proteins that are resistant to negative regulation by postnatal central nervous system antineurogenic cues.
Cédric G. Geoffroy,James A. Critchley,Diogo S. Castro,Sandra Ramelli,Christelle Barraclough,Patrick Descombes,François Guillemot,Olivier Raineteau,Olivier Raineteau +8 more
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TLDR
The results demonstrate that a better understanding of proneural protein modulation by environmental cues is a prerequisite to develop innovative approaches that will permit the manipulation of the fate of NPCs in the adult CNS after trauma or disease.Abstract:
Neural precursor cells (NPCs) are present in most regions of the adult central nervous system (CNS) Using NPCs in a therapeutical perspective, that is, to regenerate CNS tissue after injury or in neurodegenerative diseases, will require the efficient manipulation of their fate Proneural gene overexpression in NPCs represents a promising strategy to promote neuronal differentiation The activity of the proneural proteins is, however, context-dependent and can be inhibited/modulated by binding with other bHLH (basic helix-loop-helix) or HLH transcription factors In this study, we show that the two proneural proteins, Ngn2 and Mash1, are differentially sensitive to negative regulation by gliogenic factors or a gliogenic substrate (ie, postnatal spinal cord slices) Coexpressing E-proteins with proneural proteins was efficient to rescue proneural proteins neurogenic activity, suggesting a central role for E-protein sequestration in mediating postnatal CNS gliogenic inhibition Tethering of proneural proteins with E47 further insulated Mash1 from negative environmental influences whereas this strategy was not successful with Ngn2, suggesting that mechanisms of inhibition differ in between these two proneural proteins Our results demonstrate that a better understanding of proneural protein modulation by environmental cues is a prerequisite to develop innovative approaches that will permit the manipulation of the fate of NPCs in the adult CNS after trauma or diseaseread more
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A novel function of the proneural factor Ascl1 in progenitor proliferation identified by genome-wide characterization of its targets
Diogo S. Castro,Ben Martynoga,Carlos Parras,Vidya Ramesh,Emilie Pacary,Caroline Johnston,Daniela Drechsel,Melanie Lebel-Potter,Laura Galinanes Garcia,Charles Hunt,Dirk Dolle,Angela Bithell,Laurence Ettwiller,Noel J. Buckley,François Guillemot +14 more
TL;DR: A novel and unexpected activity of the proneural gene Ascl1 is identified, and a direct molecular link between the phase of expansion of neural progenitors and the subsequent phases of cell cycle exit and neuronal differentiation is revealed.
Journal ArticleDOI
Ascl1 Coordinately Regulates Gene Expression and the Chromatin Landscape during Neurogenesis
Alexandre A.S.F. Raposo,Francisca F. Vasconcelos,Daniela Drechsel,Corentine Marie,Caroline Johnston,Dirk Dolle,Dirk Dolle,Angela Bithell,Sébastien Gillotin,Debbie L. C. van den Berg,Laurence Ettwiller,Paul Flicek,Paul Flicek,Gregory E. Crawford,Carlos Parras,Benedikt Berninger,Benedikt Berninger,Noel J. Buckley,François Guillemot,Diogo S. Castro +19 more
TL;DR: A function of AsCl1 is revealed in promoting chromatin accessibility during neurogenesis, linking the chromatin landscape at Ascl1 target regions with the temporal progression of its transcriptional program.
Journal ArticleDOI
Proneural genes in neocortical development
TL;DR: Current efforts to better understand how proneural gene function is regulated will not only improve the understanding of neocortical development, but are also critical to the future development of regenerative therapies for the treatment of neuronal degeneration or disease.
Journal ArticleDOI
High Hes1 expression and resultant Ascl1 suppression regulate quiescent vs. active neural stem cells in the adult mouse brain
TL;DR: It is shown that in quiescent neural stem cells, Hes1 levels are oscillatory, although the peaks and troughs are higher than those in active neural stem Cells, causing Ascl1 expression to be continuously suppressed.
Journal ArticleDOI
Promotion of neuronal differentiation of neural progenitor cells by using EGFR antibody functionalized collagen scaffolds for spinal cord injury repair
Xiaoran Li,Zhifeng Xiao,Jin Han,Lei Chen,Hanshan Xiao,Fukai Ma,Xianglin Hou,Xing Li,Jie Sun,Wenyong Ding,Yannan Zhao,Bing Chen,Jianwu Dai +12 more
TL;DR: A well-functionalized scaffold was constructed to improve the recovery of SCI, which could promote the neuronal differentiation of neural progenitor cells in vivo.
References
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Mammalian neural stem cells.
TL;DR: Before the full potential of neural stem cells can be realized, the authors need to learn what controls their proliferation, as well as the various pathways of differentiation available to their daughter cells.
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The protein Id: A negative regulator of helix-loop-helix DNA binding proteins
Robert Benezra,Robert L. Davis,Robert L. Davis,Daniel Lockshon,David L. Turner,Harold Weintraub +5 more
TL;DR: It is proposed that HLH proteins lacking a basic region may negatively regulate other HLHprotein through the formation of nonfunctional heterodimeric complexes.
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Interactions between heterologous helix-loop-helix proteins generate complexes that bind specifically to a common DNA sequence.
Cornelis Murre,Patrick S. McCaw,H. Vaessin,M. Caudy,Lily Yeh Jan,Yuh Nung Jan,Carlos V. Cabrera,Jean N. Buskin,Stephen D. Hauschka,Andrew B. Lassar,Harold Weintraub,David Baltimore +11 more
TL;DR: The HLH domain can mediate heterodimer formation between either daughterless, E12, or E47 and achaete-scute T3 or MyoD to form proteins with high affinity for the kappa E2 site in the immunoglobulin kappa chain enhancer.
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Noggin antagonizes BMP signaling to create a niche for adult neurogenesis
Daniel A. Lim,Anthony D. Tramontin,Jose M. Trevejo,Daniel G. Herrera,José Manuel García-Verdugo,Arturo Alvarez-Buylla +5 more
TL;DR: It is proposed that ependymal Noggin production creates a neurogenic environment in the adjacent SVZ by blocking endogenous BMP signaling.