A novel conserved enhancer at zebrafish zic3 and zic6 loci drives neural expression

Dev Dyn. 2019 Sep;248(9):837-849. doi: 10.1002/dvdy.69. Epub 2019 Jun 24.

Abstract

Background: Identifying enhancers and deciphering their putative roles represent a major step to better understand the mechanism of metazoan gene regulation, development, and the role of regulatory elements in disease. Comparative genomics and transgenic assays have been used with some success to identify critical regions that are involved in regulating the spatiotemporal expression of genes during embryogenesis.

Results: We identified two novel tetrapod-teleost conserved noncoding elements within the vicinity of the zic3 and zic6 loci in the zebrafish genome and demonstrated their ability to drive tissue-specific expression in a transgenic zebrafish assay. The syntenic analysis and robust green fluorescent expression in the developing habenula in the stable transgenic line were correlated with known sites of endogenous zic3 and zic6 expression.

Conclusion: This transgenic line that expresses green fluorescent protein in the habenula is a valuable resource for studying a specific population of cells in the zebrafish central nervous system. Our observations indicate that a genomic sequence that is conserved between humans and zebrafish acts as an enhancer that likely controls zic3 and zic6 expression.

Keywords: cis-regulation; conserved noncoding elements; development; gene regulation; habenula; transgenic zebrafish.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Conserved Sequence
  • Embryonic Development / genetics
  • Enhancer Elements, Genetic*
  • Gene Expression Regulation, Developmental*
  • Green Fluorescent Proteins / metabolism
  • Habenula / embryology
  • Habenula / growth & development
  • Homeodomain Proteins / genetics*
  • Humans
  • Nervous System / metabolism*
  • Repressor Proteins / genetics*
  • Transcription Factors / genetics*
  • Zebrafish
  • Zebrafish Proteins / genetics*

Substances

  • Homeodomain Proteins
  • Repressor Proteins
  • Transcription Factors
  • Zebrafish Proteins
  • Zic6 protein, zebrafish
  • zic3 protein, zebrafish
  • Green Fluorescent Proteins