Neucrin, a novel secreted antagonist of canonical Wnt signaling, plays roles in developing neural tissues in zebrafish

Mech Dev. Jan-Feb 2012;128(11-12):577-90. doi: 10.1016/j.mod.2012.01.001. Epub 2012 Jan 12.

Abstract

Wnt signaling plays crucial roles in neural development. We previously identified Neucrin, a neural-specific secreted antagonist of canonical Wnt/β-catenin signaling, in humans and mice. Neucrin has one cysteine-rich domain, in which the positions of 10 cysteine residues are similar to those in the second cysteine-rich domain of Dickkopfs, secreted Wnt antagonists. Here, we have identified zebrafish neucrin to understand its roles in vivo. Zebrafish Neucrin also has one cysteine-rich domain, which is significantly similar to that of mouse Neucrin. Zebrafish neucrin was also predominantly expressed in developing neural tissues. To examine roles of neucrin in neural development, we analyzed neucrin knockdown embryos. Neural development in zebrafish embryos was impaired by the knockdown of neucrin. The knockdown of neucrin caused increased expression of the Wnt/β-catenin target genes. In contrast, overexpression of neucrin reduced the expression of the Wnt/β-catenin target genes. The knockdown of neucrin affected specification of dorsal region in the midbrain and hindbrain. The knockdown of neucrin also suppressed neuronal differentiation and caused increased cell proliferation and apoptosis in developing neural tissues. Neucrin is a unique secreted Wnt antagonist that is predominantly expressed in developing neural tissues and plays roles in neural development in zebrafish.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Apoptosis
  • Axin Protein / genetics
  • Axin Protein / metabolism
  • Brain / cytology
  • Brain / embryology
  • Brain / metabolism
  • Cell Proliferation
  • Cell Survival
  • Cyclin D1 / genetics
  • Cyclin D1 / metabolism
  • Gene Expression
  • Gene Knockdown Techniques
  • Molecular Sequence Data
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Nerve Tissue Proteins / physiology*
  • Neural Tube / cytology
  • Neural Tube / metabolism
  • Neurogenesis*
  • Neurons / metabolism
  • Neurons / physiology
  • Sequence Homology, Amino Acid
  • Wnt Signaling Pathway*
  • Zebrafish / embryology*
  • Zebrafish / genetics
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism
  • Zebrafish Proteins / physiology*

Substances

  • Axin Protein
  • Nerve Tissue Proteins
  • Zebrafish Proteins
  • draxin protein, zebrafish
  • Cyclin D1