The let-7 microRNA target gene, Mlin41/Trim71 is required for mouse embryonic survival and neural tube closure.
In the nematode Caenorhabditis elegans, the let-7 microRNA (miRNA) controls the timing of key developmental events and terminal differentiation in part by directly regulating lin-41. C. elegans lin-41 mutants display precocious cell cycle exit and terminal differentiation of epidermal skin cells. lin-41 orthologues are found in more complex organisms including both mice and humans, but their roles are not known. We generated Mlin41 mouse mutants to ascertain a functional role for Mlin41. Strong loss of function Mlin41 gene-trap mutants demonstrated a striking neural tube closure defect during development, and embryonic lethality. Like C. elegans lin-41, Mlin41 also appears to be regulated by the let-7 and mir-125 miRNAs. Since Mlin41 is required for neural tube closure and survival it points to human lin-41 (HLIN41/TRIM71) as a potential human development and disease gene.
Maller Schulman
Betsy R
BR
Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut, USA.
Liang
Xianping
X
Stahlhut
Carlos
C
DelConte
Casey
C
Stefani
Giovanni
G
Slack
Frank J
FJ
D000818:Animals; D005804:Genes, Lethal; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000378:metabolism*; D009154:Mutation; D054259:Neural Tube / Q000196:embryology*; D014157:Transcription Factors / Q000235:genetics*
C511366:LIN-41 protein, mouse; D035683:MicroRNAs; D014157:Transcription Factors; C487931:mirnlet7 microRNA, human