Characterization of the proneural gene regulatory network during mouse telencephalon development

Gohlke, Julia M.; Armant, Olivier; Parham, Frederick; Smith, Marjolein V.; Zimmer, Céline; Castro, Diogo S.; Nguyen, Laurent; Parker, Joel S.; Gradwohl, Gérard; Portier, Christopher J.; Guillemot, François

doi:10.1186/1741-7007-6-15

Cited by 99 publications

(91 citation statements)

References 88 publications

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“…Our work demonstrates that manipulating NvashA levels affects the gene expression of the NvanthoRFamide neurotransmitter, the Nvelav neural marker, the post-synaptic glycine receptor (PrtID127924) and the LWamide-like neural peptide 1019 RESEARCH ARTICLE NvashA regulates neurogenesis (PrtID242283), as well as two ATP-binding cassette membrane transporter genes (PrtIDs118015, 12533) associated with neural expression and function (Gohlke et al, 2008). Additionally, we observe co-expression of NvashA with the 242283 and 12533 neural genes by double fluorescent in situ hybridization, suggesting a role for NvashA in differentiating neural cells.…”

Section: Achaete-scute Proneural Genes Have a Conserved Role In Promomentioning

confidence: 94%

“…3A-H) and a multispecific anion channel transporter (ID:12533) (Fig. 3I-L) are both part of the ATP-binding cassette family of membrane transporters and are targets of the mouse achaete-scute homolog Mash1 (Ascl1 -Mouse Genome Informatics) during telencephalon development (Gohlke et al, 2008). Additionally, we identified the post-synaptic glycine neurotransmitter receptor (ID:127924) (Fig.…”

Section: Identification and Characterization Of Additional Embryonic mentioning

confidence: 99%

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Nematostella vectensis achaete-scute homolog NvashA regulates embryonic ectodermal neurogenesis and represents an ancient component of the metazoan neural specification pathway

2012

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SUMMARYachaete-scute homologs (ash) regulate neural development in all bilaterian model animals indicating that they represent a component of the ancestral neurogenic pathway. We test this by investigating four ash genes during development of a basal metazoan, the cnidarian sea anemone Nematostella vectensis. Spatiotemporal expression of ash genes in the early embryo and larval stages suggests that they regulate neurogenesis. More specifically, NvashA is co-expressed with neural genes in the embryonic ectoderm. Knockdown of NvashA results in decreased expression of eight neural markers, including the six novel neural targets identified here. Conversely, overexpression of NvashA induces increased expression of all eight genes, but only within their normal axial domains. Overexpression of NvashB-D differentially increases expression of NvashA targets. The expression patterns and differential ability of ash genes to regulate neural gene expression reveals surprising molecular complexity in these 'simple' animals. These data suggest that achaete-scute homologs functioned in the ancestral metazoan neurogenic pathway and provide a foundation to investigate further the evolution of neurogenesis and the origin of complex central nervous systems.

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Section: Achaete-scute Proneural Genes Have a Conserved Role In Promomentioning

confidence: 94%

Section: Identification and Characterization Of Additional Embryonic mentioning

confidence: 99%

Nematostella vectensis achaete-scute homolog NvashA regulates embryonic ectodermal neurogenesis and represents an ancient component of the metazoan neural specification pathway

2012

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“…As such, cortical neurogenesis is tightly regulated by a complex array of transcription factors that work in concert to coordinate NPC maintenance and differentiation. Proneural transcription factors, such as neurogenin (Neurog) and NeuroD, act as the primary initiators of differentiation through their direct regulation of target genes associated with cytoskeletal reorganization, migration, and other critical differentiation processes (3,4). Proneural transcription factors are themselves subject to transcriptional regulation by other cortical transcription factors, such as Pax6 and Hes1.…”

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confidence: 99%

The doublesex-related Dmrta2 safeguards neural progenitor maintenance involving transcriptional regulation of Hes1

Young

Keruzore

Nan

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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The mechanisms that determine whether a neural progenitor cell (NPC) reenters the cell cycle or exits and differentiates are pivotal for generating cells in the correct numbers and diverse types, and thus dictate proper brain development. Combining gain-of-function and loss-of-function approaches in an embryonic stem cell-derived cortical differentiation model, we report that doublesex-and mab-3-related transcription factor a2 (Dmrta2, also known as Dmrt5) plays an important role in maintaining NPCs in the cell cycle. Temporally controlled expression of transgenic Dmrta2 in NPCs suppresses differentiation without affecting their neurogenic competence. In contrast, Dmrta2 knockout accelerates the cell cycle exit and differentiation into postmitotic neurons of NPCs derived from embryonic stem cells and in Emx1-cre conditional mutant mice. Dmrta2 function is linked to the regulation of Hes1 and other proneural genes, as demonstrated by genome-wide RNA-seq and direct binding of Dmrta2 to the Hes1 genomic locus. Moreover, transient Hes1 expression rescues precocious neurogenesis in Dmrta2 knockout NPCs. Our study thus establishes a link between Dmrta2 modulation of Hes1 expression and the maintenance of NPCs during cortical development.Dmrta2 | Hes1 | cell cycle | transcription factor | neurogenesis

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“…To monitor progenitor progression and exit, we tested Mash-1, a proneural master gene and marker of progenitor progression (Gohlke et al, 2008). Mash-1 was not expressed in normal undifferentiated P19 stem cells, highly expressed by day 4 and normally disappeared by terminal differentiation (Figure 4, MASH-1).…”

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confidence: 99%

Loss of a cohesin-linked suppressor APRIN (Pds5b) disrupts stem cell programs in embryonal carcinoma: an emerging cohesin role in tumor suppression

et al. 2010

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Cohesins appear to have critical functions beyond mitotic cohesion. Our data on a cohesin-associated Pds5-paralog, APRIN, indicate a novel cohesin role in stem cell differentiation. APRIN/Pds5B is lost in many cancers and it is a putative tumor suppressor. Its mutations in the germ line, however, generate birth defects. We reasoned that as both cancer and birth defects share disrupted stem cell differentiation, the data suggest an APRIN/Pds5B cohesin function in stem cells. We used an embryonal carcinoma stem cell model and show here that (i) APRIN expression is precisely coordinated with stem cell differentiation; (ii) this coordination involves surface-contact and endocrine pathways; and (iii) APRIN/Pds5b coordination is critical in stem/progenitor exit decisions. APRIN knockdown disrupted Oct4, Nanog and SOX2 patterns, differentiation failed and the resulting immature proliferative cells did not progress beyond proneural progenitor phase. Furthermore, the phenotype-blocked progenitor exit (Mash-1 þ ); failed E-cadherin exit (E-Cadh low þ ); incomplete N-cadherin transition (N-Cadh low þ ); retained proliferative capacity (c-myc þ ); irregular stemness (SOX2 late þ þ ) and lost response to contact and hormonal cues-shares similarities with cancer-initiating cells. The data suggest novel APRIN/Pds5B-linked cohesin roles in stem/progenitor programs and a new mechanism in tumor suppression.

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Characterization of the proneural gene regulatory network during mouse telencephalon development

Abstract: Background: The proneural proteins Mash1 and Ngn2 are key cell autonomous regulators of neurogenesis in the mammalian central nervous system, yet little is known about the molecular pathways regulated by these transcription factors.

Cited by 99 publications

References 88 publications

Nematostella vectensis achaete-scute homolog NvashA regulates embryonic ectodermal neurogenesis and represents an ancient component of the metazoan neural specification pathway

Nematostella vectensis achaete-scute homolog NvashA regulates embryonic ectodermal neurogenesis and represents an ancient component of the metazoan neural specification pathway

The doublesex-related Dmrta2 safeguards neural progenitor maintenance involving transcriptional regulation of Hes1

Loss of a cohesin-linked suppressor APRIN (Pds5b) disrupts stem cell programs in embryonal carcinoma: an emerging cohesin role in tumor suppression

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