title: Macrophage migration inhibitory factor acts as a neurotrophin in the developing inner ear.
abstract: This study is the first to demonstrate that macrophage migration inhibitory factor (MIF), an immune system 'inflammatory' cytokine that is released by the developing otocyst, plays a role in regulating early innervation of the mouse and chick inner ear. We demonstrate that MIF is a major bioactive component of the previously uncharacterized otocyst-derived factor, which directs initial neurite outgrowth from the statoacoustic ganglion (SAG) to the developing inner ear. Recombinant MIF acts as a neurotrophin in promoting both SAG directional neurite outgrowth and neuronal survival and is expressed in both the developing and mature inner ear of chick and mouse. A MIF receptor, CD74, is found on both embryonic SAG neurons and adult mouse spiral ganglion neurons. Mif knockout mice are hearing impaired and demonstrate altered innervation to the organ of Corti, as well as fewer sensory hair cells. Furthermore, mouse embryonic stem cells become neuron-like when exposed to picomolar levels of MIF, suggesting the general importance of this cytokine in neural development.
authors.affiliation: Department of Cell and Developmental Biology, University of Michigan Medical School, 3728 BSRB 109, Zina Pitcher Place, Ann Arbor, MI 48109-2200, USA.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Bank
authors.forename: Lynne M
authors.initials: LM
authors.lastname: Bianchi
authors.forename: Fumi
authors.initials: F
authors.lastname: Ebisu
authors.forename: Dov
authors.initials: D
authors.lastname: Lerman-Sinkoff
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Smiley
authors.forename: Yu-chi
authors.initials: YC
authors.lastname: Shen
authors.forename: Poornapriya
authors.initials: P
authors.lastname: Ramamurthy
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Thompson
authors.forename: Therese M
authors.initials: TM
authors.lastname: Roth
authors.forename: Christine R
authors.initials: CR
authors.lastname: Beck
authors.forename: Matthew
authors.initials: M
authors.lastname: Flynn
authors.forename: Ryan S
authors.initials: RS
authors.lastname: Teller
authors.forename: Luming
authors.initials: L
authors.lastname: Feng
authors.forename: G Nicholas
authors.initials: GN
authors.lastname: Llewellyn
authors.forename: Brandon
authors.initials: B
authors.lastname: Holmes
authors.forename: Cyrrene
authors.initials: C
authors.lastname: Sharples
authors.forename: Jaeda
authors.initials: J
authors.lastname: Coutinho-Budd
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Linn
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Chervenak
authors.forename: David F
authors.initials: DF
authors.lastname: Dolan
authors.forename: Jennifer
authors.initials: J
authors.lastname: Benson
authors.forename: Ariane
authors.initials: A
authors.lastname: Kanicki
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Martin
authors.forename: Richard
authors.initials: R
authors.lastname: Altschuler
authors.forename: Alisa E
authors.initials: AE
authors.lastname: Koch
authors.forename: Alicia E
authors.initials: AE
authors.lastname: Koch
authors.forename: Ethan M
authors.initials: EM
authors.lastname: Jewett
authors.forename: John A
authors.initials: JA
authors.lastname: Germiller
authors.forename: Kate F
authors.initials: KF
authors.lastname: Barald
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D007758:Ear, Inner / Q000187:drug effects / Q000196:embryology* / Q000254:growth & development / Q000378:metabolism; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D016501:Neurites / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D009925:Organ of Corti / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D013136:Spiral Ganglion / Q000196:embryology / Q000254:growth & development / Q000378:metabolism
chemical_list: D008263:Macrophage Migration-Inhibitory Factors; D009414:Nerve Growth Factors; D019746:Intramolecular Oxidoreductases; C076231:Mif protein, mouse