A Knock-in Zebrafish Reporter Line for Live Visualization of Endogenous Olig2 Protein Dynamics

Zebrafish. 2025 Oct;22(5):182-188. doi: 10.1177/15458547251376166. Epub 2025 Sep 24.

Abstract

The transcription factor oligodendrocyte transcription factor 2 (Olig2) plays a central role in specifying motor neurons and oligodendrocytes during vertebrate neural development. While transgenic reporter lines such as TgBAC(olig2:EGFP) have been instrumental in visualizing olig2 expression, they fall short in directly reporting endogenous protein levels and may not fully recapitulate native gene regulation. To address these limitations, we generated a TgKI(olig2-mNeonGreen) zebrafish line using CRISPR/Cas9-mediated knock-in at the endogenous olig2 locus. The resulting Olig2-mNeonGreen fusion protein localizes specifically to the nucleus, enabling direct live imaging and accurate quantification of Olig2-expressing cells. We confirmed that the knock-in preserves endogenous mRNA expression and protein function, and that homozygous fish develop normally. As proof of concept, modulation of Sonic Hedgehog signaling altered Olig2-mNeonGreen+ cell numbers as expected, confirming the reporter's responsiveness to known upstream inputs. This TgKI(olig2-mNeonGreen) line offers a robust tool for studying neural progenitor dynamics in vivo.

Keywords: CRISPR/Cas9; Olig2; knock-in; neural progenitor; pMN.

MeSH terms

  • Animals
  • Animals, Genetically Modified / genetics
  • Animals, Genetically Modified / metabolism
  • Gene Knock-In Techniques*
  • Genes, Reporter*
  • Oligodendrocyte Transcription Factor 2* / genetics
  • Oligodendrocyte Transcription Factor 2* / metabolism
  • Zebrafish Proteins* / genetics
  • Zebrafish Proteins* / metabolism
  • Zebrafish* / genetics
  • Zebrafish* / metabolism

Substances

  • Oligodendrocyte Transcription Factor 2
  • Zebrafish Proteins
  • olig2 protein, zebrafish