Open AccessLin28-mediated promotion of protein synthesis is critical for neural progenitor cell maintenance and brain development in mice
Author(s) -
Stephanie Herrlinger,
Qiang Shao,
Mei Yang,
Qing Chang,
Yang Liu,
Xiaohan Pan,
Hang Yin,
Liwei Xie,
Jianfu Chen
Publication year - 2019
Publication title -
development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.754
H-Index - 325
eISSN - 1477-9129
pISSN - 0950-1991
DOI - 10.1242/dev.173765
Subject(s) - biology , progenitor cell , progenitor , neural stem cell , lin28 , microbiology and biotechnology , neural development , neuroscience , stem cell , transcription factor , genetics , gene , sox2
Neural progenitor cells (NPCs) undergo rapid proliferation during neurulation. This rapid growth generates a high demand for mRNA translation in a timing-dependent manner, but its underlying mechanism remains poorly understood. Lin28 is an RNA-binding protein with two paralogs, Lin28a and Lin28b, in mammals. Mice with Lin28b deletion exhibit no developmental defects, whereas we have previously reported that Lin28a deletion leads to microcephaly. Here, we find that Lin28a/b double knockout (dKO) mice display neural tube defects (NTDs) coupled with reduced proliferation and precocious differentiation of NPCs. Using ribosomal protein 24 hypomorphic mice ( Rpl24 Bst/+ ) as a genetic tool to dampen global protein synthesis, we found that Lin28a -/- ;Rpl24 Bst/+ compound mutants exhibited NTDs resembling those seen in Lin28a/b dKO mice. Increased NPC numbers and brain sizes in Lin28a-overexpressing mice were rescued by Rpl24 Bst/+ heterozygosity. Mechanistically, polysome profiling revealed reduced translation of genes involved in the regulation of cell cycle, ribosome biogenesis and translation in dKO mutants. Ribosome biogenesis was reduced in dKO and increased in Lin28a-overexpressing NPCs. Therefore, Lin28-mediated promotion of protein synthesis is essential for NPC maintenance and early brain development.