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Molecular Brain
Published in: Molecular Brain 1/2014

Open Access 01-12-2014 | Research

Identification of transcriptional regulatory elements for Ntng1 and Ntng2 genes in mice

Authors: Kunio Yaguchi, Sachiko Nishimura-Akiyoshi, Satoshi Kuroki, Takashi Onodera, Shigeyoshi Itohara

Published in: Molecular Brain | Issue 1/2014

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Abstract

Background

Higher brain function is supported by the precise temporal and spatial regulation of thousands of genes. The mechanisms that underlie transcriptional regulation in the brain, however, remain unclear. The Ntng1 and Ntng2 genes, encoding axonal membrane adhesion proteins netrin-G1 and netrin-G2, respectively, are paralogs that have evolved in vertebrates and are expressed in distinct neuronal subsets in a complementary manner. The characteristic expression patterns of these genes provide a part of the foundation of the cortical layer structure in mammals.

Results

We used gene-targeting techniques, bacterial artificial chromosome (BAC)-aided transgenesis techniques, and in vivo enhancer assays to examine transcriptional mechanisms in vivo to gain insight into how the characteristic expression patterns of these genes are acquired. Analysis of the gene expression patterns in the presence or absence of netrin-G1 and netrin-G2 functional proteins allowed us to exclude the possibility that a feedback or feedforward mechanism mediates their characteristic expression patterns. Findings from the BAC deletion series revealed that widely distributed combinations of cis-regulatory elements determine the differential gene expression patterns of these genes and that major cis-regulatory elements are located in the 85–45 kb upstream region of Ntng2 and in the 75–60 kb upstream region and intronic region of Ntng1. In vivo enhancer assays using 2-kb evolutionarily conserved regions detected enhancer activity in the distal upstream regions of both genes.

Conclusions

The complementary expression patterns of Ntng1 and Ntng2 are determined by transcriptional cis-regulatory elements widely scattered in these loci. The cis-regulatory elements characterized in this study will facilitate the development of novel genetic tools for functionally dissecting neural circuits to better understand vertebrate brain function.
Appendix
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Metadata
Title
Identification of transcriptional regulatory elements for Ntng1 and Ntng2 genes in mice
Authors
Kunio Yaguchi
Sachiko Nishimura-Akiyoshi
Satoshi Kuroki
Takashi Onodera
Shigeyoshi Itohara
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Molecular Brain / Issue 1/2014
Electronic ISSN: 1756-6606
DOI
https://doi.org/10.1186/1756-6606-7-19

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