The role of jab1, a putative downstream effector of the neurotrophic cytokine macrophage migration inhibitory factor (MIF) in zebrafish inner ear hair cell development

Exp Neurol. 2018 Mar;301(Pt B):100-109. doi: 10.1016/j.expneurol.2017.09.009. Epub 2017 Sep 18.

Abstract

Macrophage migration inhibitory factor (MIF) is a neurotrophic cytokine essential for inner ear hair cell (HC) development and statoacoustic ganglion (SAG) neurite outgrowth, and SAG survival in mouse, chick and zebrafish. Another neurotrophic cytokine, Monocyte chemoattractant protein 1 (MCP1) is known to synergize with MIF; but MCP1 alone is insufficient to support mouse/chick SAG neurite outgrowth or neuronal survival. Because of the relatively short time over which the zebrafish inner ear develops (~30hpf), the living zebrafish embryo is an ideal system to examine mif and mcp1 cytokine pathways and interactions. We used a novel technique: direct delivery of antisense oligonucleotide morpholinos (MOs) into the embryonic zebrafish otocyst to discover downstream effectors of mif as well as to clarify the relationship between mif and mcp1 in inner ear development. MOs for mif, mcp1 and the presumptive mif and mcp1 effector, c-Jun activation domain-binding protein-1 (jab1), were injected and then electroporated into the zebrafish otocyst 25-48hours post fertilization (hpf). We found that although mif is important at early stages (before 30hpf) for auditory macular HC development, jab1 is more critical for vestibular macular HC development before 30hpf. After 30hpf, mcp1 becomes important for HC development in both maculae.

Keywords: Hair cell development; Inner ear; Mif; Neurotrophic cytokines; Statoacoustic ganglion; VIII nerve; Zebrafish; jab1; mcp1.

MeSH terms

  • Acoustic Maculae / embryology
  • Acoustic Maculae / growth & development
  • Actins / metabolism
  • Animals
  • Axons / drug effects
  • COP9 Signalosome Complex / genetics
  • COP9 Signalosome Complex / physiology*
  • Chemokine CCL2 / metabolism
  • Cytokines / biosynthesis
  • Embryo, Nonmammalian
  • Hair Cells, Auditory, Inner / physiology*
  • Macrophage Migration-Inhibitory Factors / genetics
  • Macrophage Migration-Inhibitory Factors / physiology*
  • Oligonucleotides, Antisense / pharmacology
  • Oocysts / growth & development
  • Saccule and Utricle / embryology
  • Saccule and Utricle / growth & development
  • Tubulin / metabolism
  • Zebrafish

Substances

  • Actins
  • Chemokine CCL2
  • Cytokines
  • Macrophage Migration-Inhibitory Factors
  • Oligonucleotides, Antisense
  • Tubulin
  • COP9 Signalosome Complex