Lin28 promotes the proliferative capacity of neural progenitor cells in brain development

Mei Yang, Si Lu Yang, Stephanie Herrlinger, Chen Liang, Monika Dzieciatkowska, Kirk C. Hansen, Ridham Desai, Andras Nagy, Lee Niswander, Eric G. Moss, Jian Fu Chen

Research output: Contribution to journalArticleResearchpeer-review

70 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1616-1627
Number of pages12
JournalDevelopment
Volume142
Issue number9
DOIs
Publication statusPublished - 2015
Externally publishedYes

Keywords

  • Brain development
  • Lin28a
  • Lin28b
  • Mouse
  • Neural progenitor cells
  • Proliferation

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