Wnt/β-catenin signaling promotes neurogenesis in the diencephalospinal dopaminergic system of embryonic zebrafish

Sci Rep. 2022 Jan 19;12(1):1030. doi: 10.1038/s41598-022-04833-8.


Wnt/β-catenin signaling contributes to patterning, proliferation, and differentiation throughout vertebrate neural development. Wnt/β-catenin signaling is important for mammalian midbrain dopaminergic neurogenesis, while little is known about its role in ventral forebrain dopaminergic development. Here, we focus on the A11-like, Otp-dependent diencephalospinal dopaminergic system in zebrafish. We show that Wnt ligands, receptors and extracellular antagonist genes are expressed in the vicinity of developing Otp-dependent dopaminergic neurons. Using transgenic Wnt/β-catenin-reporters, we found that Wnt/β-catenin signaling activity is absent from these dopaminergic neurons, but detected Wnt/β-catenin activity in cells adjacent to the caudal DC5/6 clusters of Otp-dependent dopaminergic neurons. Pharmacological manipulations of Wnt/β-catenin signaling activity, as well as heat-shock driven overexpression of Wnt agonists and antagonists, interfere with the development of DC5/6 dopaminergic neurons, such that Wnt/β-catenin activity positively correlates with their number. Wnt/β-catenin activity promoted dopaminergic development specifically at stages when DC5/6 dopaminergic progenitors are in a proliferative state. Our data suggest that Wnt/β-catenin signaling acts in a spatially and temporally restricted manner on proliferative dopaminergic progenitors in the hypothalamus to positively regulate the size of the dopaminergic neuron groups DC5 and DC6.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Cell Differentiation
  • Dopaminergic Neurons / metabolism*
  • Gene Expression Regulation, Developmental
  • Mesencephalon / embryology
  • Mesencephalon / metabolism
  • Neurogenesis*
  • Wnt Signaling Pathway*
  • Zebrafish / embryology*
  • Zebrafish / genetics
  • beta Catenin / metabolism*


  • beta Catenin