Abstract
Notch signalling regulates a wide range of developmental processes. In the Drosophila peripheral nervous system, Notch regulates a series of binary fate decisions that lead to the formation of regularly spaced sensory organs. Each sensory organ is generated by single sensory organ precursor cell (SOP) via a series of asymmetric cell divisions. Starting from a SOP-specific Cis-Regulatory Module (CRM), we identified insensible (insb), a.k.a CG6520, as a SOP/neuron-specific gene encoding a nuclear factor that inhibits Notch signalling activity. First, over-expression of Insb led to the transcriptional repression of a Notch reporter and to phenotypes associated with the inhibition of Notch. Second, while the complete loss of insb activity had no significant phenotype, it enhanced the bristle phenotype associated with reduced levels of Hairless, a nuclear protein acting as a co-repressor for Suppressor of Hairless. In conclusion, our work identified Insb as a novel SOP/neuron-specific nuclear inhibitor of Notch activity in Drosophila.
Highlights
Cell fate decisions and patterning events during development are regulated by cell-cell interactions that are in part mediated by Notch receptors [1]
Insensible is a SOP-specific Nuclear Protein In a previous study, we used an in silico approach to identify cisregulatory modules (CRM) regulating gene expression in sensory organ precursor cells (SOPs) in Drosophila [24]
This work led to the identification of a Cis-Regulatory Module (CRM) just 59 to the gene CG6520/insensible (Figure 1A) which was active in SOPs and other neural progenitor cells
Summary
Cell fate decisions and patterning events during development are regulated by cell-cell interactions that are in part mediated by Notch receptors [1]. Trans-membrane receptors of the Notch family can be described as membrane-tethered transcriptional regulators [2]. These receptors consist in a ligand-binding ectodomain linked via a trans-membrane domain to an intracellular domain that acts as a transcriptional regulator upon its ligand-dependent release from the membrane. Following the release of the Notch Intra-Cellular Domain (NICD), the activated nuclear form of Notch [2], NICD forms a ternary complex with CSL (CBF1, Suppressor of Hairless, Lag-1), a sequence-specific DNA-binding protein known as Suppressor of Hairless [Su(H)] in flies, and a co-activator, known as Mastermind (Mam) in flies, to regulate the expression of Notch target genes. NICD increases the occupancy of CSL binding sites, relieves the transcriptional repression mediated by CSL factors and promotes transcriptional activation [2,3,9,14]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
