Brain-wide cellular resolution imaging of Cre transgenic zebrafish lines for functional circuit-mapping

Elife. 2019 Feb 8:8:e42687. doi: 10.7554/eLife.42687.

Abstract

Decoding the functional connectivity of the nervous system is facilitated by transgenic methods that express a genetically encoded reporter or effector in specific neurons; however, most transgenic lines show broad spatiotemporal and cell-type expression. Increased specificity can be achieved using intersectional genetic methods which restrict reporter expression to cells that co-express multiple drivers, such as Gal4 and Cre. To facilitate intersectional targeting in zebrafish, we have generated more than 50 new Cre lines, and co-registered brain expression images with the Zebrafish Brain Browser, a cellular resolution atlas of 264 transgenic lines. Lines labeling neurons of interest can be identified using a web-browser to perform a 3D spatial search (zbbrowser.com). This resource facilitates the design of intersectional genetic experiments and will advance a wide range of precision circuit-mapping studies.

Keywords: Cre; Gal4; brain atlas; imaging; intersectional genetics; neuroscience; registration; zebrafish.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified / genetics
  • Brain / physiology
  • Brain / ultrastructure*
  • Brain Mapping / methods*
  • Cell Lineage / genetics
  • DNA-Binding Proteins / genetics
  • Gene Expression Regulation / genetics
  • Integrases / genetics
  • Neuroimaging / methods*
  • Neurons / physiology
  • Neurons / ultrastructure*
  • Transcription Factors / genetics
  • Zebrafish / genetics
  • Zebrafish / physiology

Substances

  • DNA-Binding Proteins
  • Transcription Factors
  • Cre recombinase
  • Integrases