title: Nemo promotes Notch-mediated lateral inhibition downstream of proneural factors.
abstract: During neurogenesis, conserved tissue-specific proneural factors establish a cell's competence to take on neural fate from within a field of unspecified cells. Proneural genes encode basic helix-loop-helix transcription factors that promote the expression of 'core' and subtype-specific target genes. Target genes include both pan-neuronal genes and genes that aid in the process of refinement, known as lateral inhibition. In this process, proneural gene expression is increased in the neural progenitor while simultaneously down-regulated in the surrounding cells, in a Notch signalling-dependent manner. Here, we identify nemo (nmo) as a target of members of both Drosophila Atonal and Achaete-Scute proneural factor families and find that mammalian proneural homologs induce Nemo-like-kinase (Nlk) expression in cell culture. We find that nmo loss of function leads to reduced expression of Notch targets and to perturbations in Notch-mediated lateral inhibition. Furthermore, Notch hyperactivity can compensate for nmo loss in the Drosophila eye. Thus nmo promotes Notch-mediated lateral inhibition downstream of proneural factors during neurogenesis.
authors.affiliation: Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada V5A1S6.
authors.forename: Vilaiwan M
authors.initials: VM
authors.lastname: Fernandes
authors.affiliation: Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada V5A1S6.
authors.forename: Shanker S S
authors.initials: SS
authors.lastname: Panchapakesan
authors.affiliation: Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada V5A1S6; Defence Research and Development Canada - Suffield, Biotechnology Section, Medicine Hat, AB, Canada T1A 8K6.
authors.forename: Lorena R
authors.initials: LR
authors.lastname: Braid
authors.affiliation: Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada V5A1S6. Electronic address: everheye@sfu.ca.
authors.forename: Esther M
authors.initials: EM
authors.lastname: Verheyen
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D004330:Drosophila / Q000196:embryology* / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D005123:Eye / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D055495:Neurogenesis / Q000502:physiology*; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D029721:Drosophila Proteins; D020928:Mitogen-Activated Protein Kinases; D009419:Nerve Tissue Proteins; D051880:Receptors, Notch; C497759:N protein, Drosophila; C082142:ato protein, Drosophila; C110707:nmo protein, Drosophila
keywords: Achaete-Scute; Atonal; NLK; Nemo; Notch; Proneural