Dner inhibits neural progenitor proliferation and induces neuronal and glial differentiation in zebrafish

Dev Biol. 2013 Mar 1;375(1):1-12. doi: 10.1016/j.ydbio.2013.01.007. Epub 2013 Jan 15.


Delta/notch-like epidermal growth factor (EGF)-related receptor (DNER) is a single-pass transmembrane protein found to be a novel ligand in the Notch signaling pathway. Its function was previously characterized in the developing cerebellum and inner ear hair cells. In this study, we isolated a zebrafish homolog of DNER and showed that this gene is expressed in the developing nervous system. Overexpression of dner or the intracellular domain of dner was sufficient to inhibit the proliferation of neural progenitors and induce neuronal and glial differentiation. In contrast, the knockdown of endogenous Dner expression using antisense morpholino oligonucleotides increased the proliferation of neural progenitors and maintained neural cells in a progenitor status through inhibition of neuronal and glial differentiation. Through analysis of the antagonistic effect on the Delta ligand and the role of the potential downstream mediator Deltex1, we showed that Dner acts in Notch-dependent and Notch-independent manner. This is the first study to demonstrate a role for Dner in neural progenitors and neuronal differentiation and provides new insights into mediation of neuronal development and differentiation by the Notch signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Basic Helix-Loop-Helix Transcription Factors / biosynthesis
  • Cell Proliferation
  • DNA-Binding Proteins / antagonists & inhibitors*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Gene Knockdown Techniques
  • Morpholinos
  • Nerve Tissue Proteins / biosynthesis
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Nervous System / embryology
  • Nervous System / metabolism
  • Neural Stem Cells / cytology*
  • Neural Stem Cells / physiology
  • Neurogenesis*
  • Neuroglia / cytology*
  • Neuroglia / physiology
  • Neurons / cytology*
  • Neurons / physiology
  • Oligodeoxyribonucleotides, Antisense
  • Receptors, Cell Surface / biosynthesis
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism*
  • Receptors, Notch / metabolism*
  • Sequence Alignment
  • Signal Transduction
  • Zebrafish
  • Zebrafish Proteins / antagonists & inhibitors*
  • Zebrafish Proteins / biosynthesis
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism*


  • Basic Helix-Loop-Helix Transcription Factors
  • DNA-Binding Proteins
  • Morpholinos
  • Nerve Tissue Proteins
  • Oligodeoxyribonucleotides, Antisense
  • Receptors, Cell Surface
  • Receptors, Notch
  • Zebrafish Proteins
  • delta-notch-like EGF-related receptor, zebrafish
  • deltex protein 1, zebrafish
  • dld protein, zebrafish
  • her4.1 protein, zebrafish