title: Trithorax maintains the functional heterogeneity of neural stem cells through the transcription factor buttonhead.
abstract: The mechanisms that maintain the functional heterogeneity of stem cells, which generates diverse differentiated cell types required for organogenesis, are not understood. In this study, we report that Trithorax (Trx) actively maintains the heterogeneity of neural stem cells (neuroblasts) in the developing Drosophila larval brain. trx mutant type II neuroblasts gradually adopt a type I neuroblast functional identity, losing the competence to generate intermediate neural progenitors (INPs) and directly generating differentiated cells. Trx regulates a type II neuroblast functional identity in part by maintaining chromatin in the buttonhead (btd) locus in an active state through the histone methyltransferase activity of the SET1/MLL complex. Consistently, btd is necessary and sufficient for eliciting a type II neuroblast functional identity. Furthermore, over-expression of btd restores the competence to generate INPs in trx mutant type II neuroblasts. Thus, Trx instructs a type II neuroblast functional identity by epigenetically promoting Btd expression, thereby maintaining neuroblast functional heterogeneity.
authors.affiliation: Center for Stem Cell Biology, Life Sciences Institute, University of Michigan Medical School, Ann Arbor, United States.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Komori
authors.affiliation: Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, United States.
authors.forename: Qi
authors.initials: Q
authors.lastname: Xiao
authors.affiliation: Program in Cell and Molecular Biology, University of Michigan Medical School, Ann Arbor, United States.
authors.forename: Derek H
authors.initials: DH
authors.lastname: Janssens
authors.affiliation: Department of Pathology, University of Michigan Medical School, Ann Arbor, United States.
authors.forename: Yali
authors.initials: Y
authors.lastname: Dou
authors.affiliation: Center for Stem Cell Biology, Life Sciences Institute, University of Michigan Medical School, Ann Arbor, United States.
authors.forename: Cheng-Yu
authors.initials: CY
authors.lastname: Lee
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D002454:Cell Differentiation; D019070:Cell Lineage / Q000235:genetics; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D044127:Epigenesis, Genetic; D018507:Gene Expression Regulation, Developmental; D056426:Genetic Loci; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism; D007814:Larva / Q000166:cytology / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D009154:Mutation; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D014157:Transcription Factors; C084801:btd protein, Drosophila; C512571:trx protein, Drosophila; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase; C582802:Set1 protein, Drosophila
keywords: D. melanogaster; Trithorax; developmental biology; intermediate neural progenitor; larval brain; neural stem cells; neuroblast; stem cells