MANF regulates dopaminergic neuron development in larval zebrafish

Dev Biol. 2012 Oct 15;370(2):237-49. doi: 10.1016/j.ydbio.2012.07.030. Epub 2012 Aug 7.


Mesencephalic astrocyte derived neurotrophic factor (MANF) is recognized as a dopaminergic neurotrophic factor, which can protect dopaminergic neurons from neurotoxic damage. However, little is known about the function of MANF during the vertebrate development. Here, we report that MANF expression is widespread during embryonic development and in adult organs analyzed by qPCR and in situ hybridization in zebrafish. Knockdown of MANF expression with antisense splice-blocking morpholino oligonucleotides resulted in no apparent abnormal phenotype. Nevertheless, the dopamine level of MANF morphants was lower than that of the wild type larvae, the expression levels of the two tyrosine hydroxylase gene transcripts were decreased and a decrease in neuron number in certain groups of th1 and th2 cells in the diencephalon region in MANF morphants was observed. These defects were rescued by injection of exogenous manf mRNA. Strikingly, manf mRNA could partly restore the decrease of th1 positive cells in Nr4a2-deficient larvae. These results suggest that MANF is involved in the regulation of the development of dopaminergic system in zebrafish.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / cytology
  • Brain / embryology
  • Brain / metabolism
  • Dopaminergic Neurons / cytology*
  • Dopaminergic Neurons / metabolism
  • Embryo, Nonmammalian / embryology
  • Embryo, Nonmammalian / metabolism
  • Homeodomain Proteins / metabolism
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Morpholinos / metabolism
  • Nerve Growth Factors / metabolism*
  • Nerve Tissue Proteins / metabolism
  • Neuropeptides / metabolism
  • Nuclear Receptor Subfamily 4, Group A, Member 2 / genetics
  • Nuclear Receptor Subfamily 4, Group A, Member 2 / metabolism
  • Orexins
  • PAX2 Transcription Factor / metabolism
  • Receptor, Notch1 / metabolism
  • Serotonin / metabolism
  • Transcription Factors / metabolism
  • Zebrafish / embryology*
  • Zebrafish / metabolism
  • Zebrafish Proteins / metabolism*
  • gamma-Aminobutyric Acid / metabolism


  • Ascl1a protein, zebrafish
  • Homeodomain Proteins
  • Intracellular Signaling Peptides and Proteins
  • MANF protein, zebrafish
  • Morpholinos
  • Nerve Growth Factors
  • Nerve Tissue Proteins
  • Neuropeptides
  • Nuclear Receptor Subfamily 4, Group A, Member 2
  • Orexins
  • PAX2 Transcription Factor
  • Receptor, Notch1
  • Transcription Factors
  • Zebrafish Proteins
  • notch1a protein, zebrafish
  • pax2a protein, zebrafish
  • Serotonin
  • gamma-Aminobutyric Acid