title: bHLH-O proteins are crucial for Drosophila neuroblast self-renewal and mediate Notch-induced overproliferation.
abstract: Drosophila larval neurogenesis is an excellent system for studying the balance between self-renewal and differentiation of a somatic stem cell (neuroblast). Neuroblasts (NBs) give rise to differentiated neurons and glia via intermediate precursors called GMCs or INPs. We show that E(spl)mγ, E(spl)mβ, E(spl)m8 and Deadpan (Dpn), members of the basic helix-loop-helix-Orange protein family, are expressed in NBs but not in differentiated cells. Double mutation for the E(spl) complex and dpn severely affects the ability of NBs to self-renew, causing premature termination of proliferation. Single mutations produce only minor defects, which points to functional redundancy between E(spl) proteins and Dpn. Expression of E(spl)mγ and m8, but not of dpn, depends on Notch signalling from the GMC/INP daughter to the NB. When Notch is abnormally activated in NB progeny cells, overproliferation defects are seen. We show that this depends on the abnormal induction of E(spl) genes. In fact E(spl) overexpression can partly mimic Notch-induced overproliferation. Therefore, E(spl) and Dpn act together to maintain the NB in a self-renewing state, a process in which they are assisted by Notch, which sustains expression of the E(spl) subset.
authors.affiliation: Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology Hellas, Department of Biology, University of Crete, Heraklion, Crete, Greece.
authors.forename: Evanthia
authors.initials: E
authors.lastname: Zacharioudaki
authors.forename: Srivathsa S
authors.initials: SS
authors.lastname: Magadi
authors.forename: Christos
authors.initials: C
authors.lastname: Delidakis
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D049109:Cell Proliferation; D003433:Crosses, Genetic; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D008856:Microscopy, Fluorescence / Q000379:methods; D008954:Models, Biological; D009154:Mutation; D054258:Neural Plate / Q000166:cytology; D009687:Nuclear Proteins / Q000378:metabolism*; D010641:Phenotype; D051880:Receptors, Notch / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D013997:Time Factors
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D009687:Nuclear Proteins; D051880:Receptors, Notch; D012097:Repressor Proteins; C121960:E(spl)m7-HLH protein, Drosophila; C078020:Dpn protein, Drosophila