Members of the miRNA-200 Family Regulate Olfactory Neurogenesis

Philip S Choi,Lisa Zakhary,Wen-Yee Choi,Sophie Caron,Ezequiel Alvarez-Saavedra,Eric A Miska,Mike Mcmanus,Brian Harfe,Antonio J Giraldez,Robert H Horvitz,Alexander F Schier,Catherine Dulac

doi:10.1016/j.neuron.2007.11.018

Abstract

SummaryMicroRNAs (miRNAs) are highly expressed in vertebrate neural tissues, but the contribution of specific miRNAs to the development and function of different neuronal populations is still largely unknown. We report that miRNAs are required for terminal differentiation of olfactory precursors in both mouse and zebrafish but are dispensable for proper function of mature olfactory neurons. The repertoire of miRNAs expressed in olfactory tissues contains over 100 distinct miRNAs. A subset, including the miR-200 family, shows high olfactory enrichment and expression patterns consistent with a role during olfactory neurogenesis. Loss of function of the miR-200 family phenocopies the terminal differentiation defect observed in absence of all miRNA activity in olfactory progenitors. Our data support the notion that vertebrate tissue differentiation is controlled by conserved subsets of organ-specific miRNAs in both mouse and zebrafish and provide insights into control mechanisms underlying olfactory differentiation in vertebrates.

Highlights

MicroRNAs constitute a large class of small noncoding RNAs that provide multicellular organisms with elaborate yet poorly understood strategies for posttranscriptional gene regulation (Bartel, 2004)
In order to understand the roles played by miRNAs during olfactory development, we aimed to identify the repertoire of miRNAs expressed in peripheral olfactory tissues
Reversetranscribed and amplified cDNA generated from the 18–26 nucleotide small RNA fraction of olfactory as well as from various neural and nonneural tissues dissected from newborn and adult rats were hybridized to microarrays capable of detecting the expression of 138 known mammalian miRNAs (Miska et al, 2004)

Summary

Introduction

MicroRNAs (miRNAs) constitute a large class of small noncoding RNAs that provide multicellular organisms with elaborate yet poorly understood strategies for posttranscriptional gene regulation (Bartel, 2004). The essential roles played by some miRNAs in controlling invertebrate neurogenesis and the dynamic patterns of miRNA expression during vertebrate development have raised the issue as to whether miRNAs might regulate aspects of vertebrate neural development (Miska et al, 2004; Kosik and Krichevsky, 2006; Cao et al, 2006; Makeyev et al, 2007). This question has remained unanswered because lossof-function studies of specific neural microRNAs in vertebrates have not yet been performed

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