title: Prefoldin and Pins synergistically regulate asymmetric division and suppress dedifferentiation.
abstract: Prefoldin is a molecular chaperone complex that regulates tubulin function in mitosis. Here, we show that Prefoldin depletion results in disruption of neuroblast polarity, leading to neuroblast overgrowth in Drosophila larval brains. Interestingly, co-depletion of Prefoldin and Partner of Inscuteable (Pins) leads to the formation of gigantic brains with severe neuroblast overgrowth, despite that Pins depletion alone results in smaller brains with partially disrupted neuroblast polarity. We show that Prefoldin acts synergistically with Pins to regulate asymmetric division of both neuroblasts and Intermediate Neural Progenitors (INPs). Surprisingly, co-depletion of Prefoldin and Pins also induces dedifferentiation of INPs back into neuroblasts, while depletion either Prefoldin or Pins alone is insufficient to do so. Furthermore, knocking down either α-tubulin or β-tubulin in pins(-) mutant background results in INP dedifferentiation back into neuroblasts, leading to the formation of ectopic neuroblasts. Overexpression of α-tubulin suppresses neuroblast overgrowth observed in prefoldin pins double mutant brains. Our data elucidate an unexpected function of Prefoldin and Pins in synergistically suppressing dedifferentiation of INPs back into neural stem cells.
authors.affiliation: Neuroscience &Behavioral Disorders Program, Duke-NUS Graduate Medical School Singapore, 8 College Road, Singapore 169857.|NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, 28 Medical Drive, Singapore 117456.
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institute for Research in Biomedicine (IRB-Barcelona), Baldiri Reixac 10, 08028 Barcelona, Spain.
authors.forename: Madhulika
authors.initials: M
authors.lastname: Rai
authors.affiliation: Neuroscience &Behavioral Disorders Program, Duke-NUS Graduate Medical School Singapore, 8 College Road, Singapore 169857.
authors.forename: Cheng
authors.initials: C
authors.lastname: Wang
authors.affiliation: Institute for Research in Biomedicine (IRB-Barcelona), Baldiri Reixac 10, 08028 Barcelona, Spain.|Institució Catalana de Recerca i Estudis Avançats (ICREA). Passeig Lluís Companys 23, 08010 Barcelona, Spain.
authors.forename: Cayetano
authors.initials: C
authors.lastname: Gonzalez
authors.affiliation: Neuroscience &Behavioral Disorders Program, Duke-NUS Graduate Medical School Singapore, 8 College Road, Singapore 169857.|NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, 28 Medical Drive, Singapore 117456.|Dept. of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D060049:Asymmetric Cell Division; D001921:Brain / Q000166:cytology; D018797:Cell Cycle Proteins; D054337:Cell Dedifferentiation; D002460:Cell Line; D016764:Cell Polarity; D049109:Cell Proliferation; D029721:Drosophila Proteins / Q000502:physiology*; D004331:Drosophila melanogaster / Q000166:cytology; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000502:physiology*; D006706:Homeostasis; D007814:Larva / Q000166:cytology; D018832:Molecular Chaperones / Q000502:physiology*; D058953:Neural Stem Cells
chemical_list: D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D020730:Guanine Nucleotide Dissociation Inhibitors; C572493:Mgr protein, Drosophila; D018832:Molecular Chaperones; C000614233:Pfdn2 protein, Drosophila; C405164:Pins protein, Drosophila