Lin28 promotes the proliferative capacity of neural progenitor cells in brain development.
Neural progenitor cells (NPCs) have distinct proliferation capacities at different stages of brain development. Lin28 is an RNA-binding protein with two homologs in mice: Lin28a and Lin28b. Here we show that Lin28a/b are enriched in early NPCs and their expression declines during neural differentiation. Lin28a single-knockout mice show reduced NPC proliferation, enhanced cell cycle exit and a smaller brain, whereas mice lacking both Lin28a alleles and one Lin28b allele display similar but more severe phenotypes. Ectopic expression of Lin28a in mice results in increased NPC proliferation, NPC numbers and brain size. Mechanistically, Lin28a physically and functionally interacts with Imp1 (Igf2bp1) and regulates Igf2-mTOR signaling. The function of Lin28a/b in NPCs could be attributed, at least in part, to the regulation of their mRNA targets that encode Igf1r and Hmga2. Thus, Lin28a and Lin28b have overlapping functions in temporally regulating NPC proliferation during early brain development.
Department of Genetics, Biochemistry & Molecular Biology, University of Georgia, Athens, GA 30602, USA.
Mei
M
Yang
Department of Genetics, Biochemistry & Molecular Biology, University of Georgia, Athens, GA 30602, USA.
Si-Lu
SL
Yang
Department of Genetics, Biochemistry & Molecular Biology, University of Georgia, Athens, GA 30602, USA.
Stephanie
S
Herrlinger
Department of Genetics, Biochemistry & Molecular Biology, University of Georgia, Athens, GA 30602, USA.
Chen
C
Liang
Department of Biochemistry & Molecular Genetics, University of Colorado Denver, Aurora, CO 80045, USA.
Monika
M
Dzieciatkowska
Department of Biochemistry & Molecular Genetics, University of Colorado Denver, Aurora, CO 80045, USA.
Kirk C
KC
Hansen
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON M5T 3L9, Canada.
Ridham
R
Desai
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON M5T 3L9, Canada.
Andras
A
Nagy
Department of Pediatrics, University of Colorado Anschutz Medical Campus, Children's Hospital Colorado, Aurora, CO 80045, USA.
Lee
L
Niswander
Department of Molecular Biology, Rowan University, Stratford, NJ 08084, USA.
Eric G
EG
Moss
Department of Genetics, Biochemistry & Molecular Biology, University of Georgia, Athens, GA 30602, USA chen2014@uga.edu.
Jian-Fu
JF
Chen
D000818:Animals; D001921:Brain / Q000166:cytology / Q000196:embryology*; D001973:Bromodeoxyuridine; D049109:Cell Proliferation / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018274:Electroporation; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D025743:HMGA2 Protein / Q000378:metabolism; D047468:Immunoprecipitation; D051379:Mice; D018345:Mice, Knockout; D058953:Neural Stem Cells / Q000502:physiology*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction
D004268:DNA-Binding Proteins; D025743:HMGA2 Protein; C579063:IMP1 protein, mouse; C488352:Lin-28 protein, mouse; C570876:Lin28b protein, mouse; D016601:RNA-Binding Proteins; D001973:Bromodeoxyuridine
Brain development; Lin28a; Lin28b; Mouse; Neural progenitor cells; Proliferation