Dataset Information

Differential interactions between Notch and ID factors control neurogenesis by modulating Hes factor autoregulation.

ABSTRACT: During embryonic and adult neurogenesis, neural stem cells (NSCs) generate the correct number and types of neurons in a temporospatial fashion. Control of NSC activity and fate is crucial for brain formation and homeostasis. Neurogenesis in the embryonic and adult brain differ considerably, but Notch signaling and inhibitor of DNA-binding (ID) factors are pivotal in both. Notch and ID factors regulate NSC maintenance; however, it has been difficult to evaluate how these pathways potentially interact. Here, we combined mathematical modeling with analysis of single-cell transcriptomic data to elucidate unforeseen interactions between the Notch and ID factor pathways. During brain development, Notch signaling dominates and directly regulates Id4 expression, preventing other ID factors from inducing NSC quiescence. Conversely, during adult neurogenesis, Notch signaling and Id2/3 regulate neurogenesis in a complementary manner and ID factors can induce NSC maintenance and quiescence in the absence of Notch. Our analyses unveil key molecular interactions underlying NSC maintenance and mechanistic differences between embryonic and adult neurogenesis. Similar Notch and ID factor interactions may be crucial in other stem cell systems.

SUBMITTER: Boareto M

PROVIDER: S-EPMC5665482 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Differential interactions between Notch and ID factors control neurogenesis by modulating Hes factor autoregulation.

Boareto Marcelo M Iber Dagmar D Taylor Verdon V

Development (Cambridge, England) 20171001 19

During embryonic and adult neurogenesis, neural stem cells (NSCs) generate the correct number and types of neurons in a temporospatial fashion. Control of NSC activity and fate is crucial for brain formation and homeostasis. Neurogenesis in the embryonic and adult brain differ considerably, but Notch signaling and inhibitor of DNA-binding (ID) factors are pivotal in both. Notch and ID factors regulate NSC maintenance; however, it has been difficult to evaluate how these pathways potentially inte ...[more]

PMID: 28974640

Similar Datasets

Project description:BackgroundEstablishment and maintenance of a functional central nervous system (CNS) requires a highly orchestrated process of neural progenitor cell proliferation, cell cycle exit, and differentiation. An evolutionary conserved program consisting of Notch signalling mediated by basic Helix-Loop-Helix (bHLH) transcription factor activity is necessary for both the maintenance of neural progenitor cell character and the progression of neurogenesis; however, additional players in mammalian CNS neural specification remain largely unknown. In Drosophila we recently characterized Hamlet, a transcription factor that mediates Notch signalling and neural cell fate.Methodology/principal findingsHamlet is a member of the Prdm (PRDI-BF1 and RIZ homology domain containing) proto-oncogene transcription factor family, and in this study we report that multiple genes in the Prdm family (Prdm6, 8, 12, 13 and 16) are expressed in the developing mouse CNS in a spatially and temporally restricted manner. In developing spinal cord Prdm8, 12 and 13 are expressed in precise neuronal progenitor zones suggesting that they may specify discrete neuronal subtypes. In developing telencephalon Prdm12 and 16 are expressed in the ventricular zone in a lateral to medial graded manner, and Prdm8 is expressed in a complementary domain in postmitotic neurons. In postnatal brain Prdm8 additionally shows restricted expression in cortical layers 2/3 and 4, the hippocampus, and the amygdala. To further elucidate roles of Prdm8 and 16 in the developing telencephalon we analyzed the relationship between these factors and the bHLH Hes (Hairy and enhancer of split homolog) effectors of Notch signalling. In Hes null telencephalon neural differentiation is enhanced, Prdm8 expression is upregulated, and Prdm16 expression is downregulated; conversely in utero electroporation of Hes1 into the developing telencephalon upregulates Prdm16 expression.Conclusions/significanceOur data demonstrate that Prdm genes are regulated by the Notch-Hes pathway and represent strong candidates to control neural class specification and the sequential progression of mammalian CNS neurogenesis.

Dataset Information

Differential interactions between Notch and ID factors control neurogenesis by modulating Hes factor autoregulation.

Publications

Differential interactions between Notch and ID factors control neurogenesis by modulating Hes factor autoregulation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets