Article

The development of semicircular canals in the inner ear: role of FGFs in sensory cristae

Department of Biological Sciences, Purdue University, ウェストラファイエット, Indiana, United States
Development (Impact Factor: 6.27). 10/2004; 131(17):4201-11. DOI: 10.1242/dev.01292
Source: PubMed

ABSTRACT In the vertebrate inner ear, the ability to detect angular head movements lies in the three semicircular canals and their sensory tissues, the cristae. The molecular mechanisms underlying the formation of the three canals are largely unknown. Malformations of this vestibular apparatus found in zebrafish and mice usually involve both canals and cristae. Although there are examples of mutants with only defective canals, few mutants have normal canals without some prior sensory tissue specification, suggesting that the sensory tissues, cristae, might induce the formation of their non-sensory components, the semicircular canals. We fate-mapped the vertical canal pouch in chicken that gives rise to the anterior and posterior canals, using a fluorescent, lipophilic dye (DiI), and identified a canal genesis zone adjacent to each prospective crista that corresponds to the Bone morphogenetic protein 2 (Bmp2)-positive domain in the canal pouch. Using retroviruses or beads to increase Fibroblast Growth Factors (FGFs) for gain-of-function and beads soaked with the FGF inhibitor SU5402 for loss-of-function experiments, we show that FGFs in the crista promote canal development by upregulating Bmp2. We postulate that FGFs in the cristae induce a canal genesis zone by inducing/upregulating Bmp2 expression. Ectopic FGF treatments convert some of the cells in the canal pouch from the prospective common crus to a canal-like fate. Thus, we provide the first molecular evidence whereby sensory organs direct the development of the associated non-sensory components, the semicircular canals, in vertebrate inner ears.

1 Follower
 · 
153 Views
  • Source
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Various cellular replacement therapies using in vitro generated cells to replace damaged tissue have been proposed as strategies to alleviate hearing loss. All such therapies must involve a complete understanding of the earliest steps in inner ear development; its induction as a thickened plate of cells in the non-neural, surface ectoderm of the embryo, to its internalization as an otocyst embedded in the head mesenchyme of the embryo. Such knowledge informs researchers addressing the feasibility of the proposed strategy and present alternatives if needed. In this review we describe the mechanisms of inner ear induction, concentrating on the factors that steer the fate of ectoderm into precursors of the inner ear. Induction then leads to inner ear morphogenesis and we describe the cellular changes that occur as the inner ear is converted from a superficial placode to an internalized otocyst, and how they are coordinated with a particular emphasis on how the signaling environment surrounding the inner ear influences these processes.
    Frontiers in Pharmacology 02/2015; 6. DOI:10.3389/fphar.2015.00019
  • [Show abstract] [Hide abstract]
    ABSTRACT: The membranous labyrinth of the inner ear is a highly complex organ that detects sound and balance. Developmental defects in the inner ear cause congenital hearing loss and balance disorders. The membranous labyrinth consists of three semicircular ducts, the utricle, saccule, and endolymphatic ducts, and the cochlear duct. These complex structures develop from the simple otic placode, which is established in the cranial ectoderm adjacent to the neural crest at the level of the hindbrain at the early neurula stage. During development, the otic placode invaginates to form the otic vesicle, which subsequently gives rise to neurons for the vestibulocochlear ganglion, the non-sensory and sensory epithelia of the membranous labyrinth that includes three ampullary crests, two maculae, and the organ of Corti. Combined paracrine and autocrine signals including fibroblast growth factor, Wnt, retinoic acid, hedgehog, and bone morphogenetic protein regulate fate determination, axis formation, and morphogenesis in the developing inner ear. Juxtacrine signals mediated by Notch pathways play a role in establishing the sensory epithelium, which consists of mechanosensory hair cells and supporting cells. The highly differentiated organ of Corti, which consists of uniformly oriented inner/outer hair cells and specific supporting cells, develops during fetal development. Developmental alterations/arrest causes congenital malformations in the inner ear in a spatiotemporal-restricted manner. A clearer understanding of the mechanisms underlying inner ear development is important not only for the management of patients with congenital inner ear malformations, but also for the development of regenerative therapy for impaired function.
    Congenital Anomalies 07/2014; 55(1). DOI:10.1111/cga.12072 · 0.78 Impact Factor