The cytokine macrophage migration inhibitory factor (MIF) acts as a neurotrophin in the developing inner ear of the zebrafish, Danio rerio.
Macrophage migration inhibitory factor (MIF) plays versatile roles in the immune system. MIF is also widely expressed during embryonic development, particularly in the nervous system, although its roles in neural development are only beginning to be understood. Evidence from frogs, mice and zebrafish suggests that MIF has a major role as a neurotrophin in the early development of sensory systems, including the auditory system. Here we show that the zebrafish mif pathway is required for both sensory hair cell (HC) and sensory neuronal cell survival in the ear, for HC differentiation, semicircular canal formation, statoacoustic ganglion (SAG) development, and lateral line HC differentiation. This is consistent with our findings that MIF is expressed in the developing mammalian and avian auditory systems and promotes mouse and chick SAG neurite outgrowth and neuronal survival, demonstrating key instructional roles for MIF in vertebrate otic development.
Department of Cell and Developmental Biology, Medical School, University of Michigan, Ann Arbor, MI, USA.
Yu-chi
YC
Shen
Deborah L
DL
Thompson
Meng-Kiat
MK
Kuah
Kah-Loon
KL
Wong
Karen L
KL
Wu
Stephanie A
SA
Linn
Ethan M
EM
Jewett
Alexander Chong
AC
Shu-Chien
Kate F
KF
Barald
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D007758:Ear, Inner / Q000196:embryology / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D017950:Ganglia, Sensory / Q000196:embryology / Q000378:metabolism; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006198:Hair Cells, Auditory / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006877:Hydroxamic Acids / Q000494:pharmacology; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics* / Q000378:metabolism; D009414:Nerve Growth Factors / Q000235:genetics*; D011743:Pyrimidines / Q000494:pharmacology; D011971:Receptors, Immunologic / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012665:Semicircular Canals / Q000196:embryology / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000166:cytology / Q000378:metabolism; D013997:Time Factors; D015027:Zebrafish / Q000196:embryology / Q000235:genetics*; D029961:Zebrafish Proteins / Q000235:genetics*
C532251:4-iodo-6-phenylpyrimidine; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D008263:Macrophage Migration-Inhibitory Factors; D009414:Nerve Growth Factors; D011743:Pyrimidines; D011971:Receptors, Immunologic; D029961:Zebrafish Proteins; C033184:macrophage migration inhibitory factor receptor; C012589:trichostatin A