Hindbrain signals in otic regionalization: walk on the wild side

Abstract

The inner ear, the sensory organ responsible for hearing and balance, contains specialized sensory and non-sensory epithelia arranged in a highly complex three-dimensional structure. To achieve this level of complexity, a tight coordination between morphogenesis and cell fate specification is essential during otic development. Tissues surrounding the otic primordium and more particularly the adjacent segmented hindbrain, have been implicated in conferring signals required for inner ear development. In this review, we present the current view on the role of hindbrain signals in axial specification of the inner ear. The functional analysis of mutants of hindbrain segmentation genes, as well as the investigation of signaling pathways potentially involved, all point to an essential role of FGF, Wnt and Hh signaling in otic regionalization. However, these data provide conflicting evidence regarding the involvement of hindbrain signals in otic regionalization in fish and in amniotes. We discuss the possible origin of these differences. KEY WORDS: hindbrain, patterning, otic regionalization, FGF signaling Basic structure of the adult inner earThe vertebrate inner ear is a sensory organ responsible for the senses of hearing, balance and detection of acceleration. It consists of a closed epithelial structure, the membranous labyrinth, composed of several sensory and non-sensory structures and surrounded by a bony capsule. The mechanosensory function of the inner ear is provided by the hair cells, which, along with supporting and secretory cells, are contained in the sensory epithelia. Hair cells are innervated by sensory neurons of the vestibular and acoustic ganglia that project to the vestibular and auditory nuclei in the brainstem.The membranous labyrinth is subdivided into vestibular and auditory regions. The vestibule forms the dorsal part of the labyrinth and is responsible for the senses of motion and position. It comprises the three cristae, the sensory organs located at the basis of three orthogonally arranged semi-circular canals and the utricle and saccule, which contain two additional sensory organs, the maculae. The ventral auditory part is more diverse. In mammals it is composed of the cochlea, a coiled structure whose sensory epithelium is called the organ of Corti. In birds, the auditory region is composed of the basilar papilla, while in fish the saccule and lagena are both involved in hearing (Figure 1). In jawed vertebrates, the adult inner ear is highly regionalised along its three axes. In addition to the dorso-ventral (DV) subdivision Int. J. Dev. Biol. 51: 495-506 (2007) doi: 10.1387/ijdb.072345ss into vestibular and auditory regions, an asymmetry along the medio-lateral (ML) axis is also obvious with, for instance, the endolymphatic sac and duct located in the medial part, close to the brain. The whole structure also shows pronounced anteroposterior (AP) asymmetry (Figure 1).How are these asymmetries established during ear development? What are the signals involved in establishing thes...

Her9 represses neurogenic fate downstream of Tbx1 and retinoic acid signaling in the inner ear

“…Its development commences from the otic placode, an ectodermal structure adjacent to the posterior hindbrain. Extrinsic signals from various surrounding tissues are integrated by otic-fated cells, contributing to the complex threedimensional organization of the organ and the generation of the stereotyped pattern of sensory neurons, hair cells and supporting cells (Bok et al, 2005;Schneider-Maunoury and Pujades, 2007;Whitfield and Hammond, 2007). The generation of sensory neurons is restricted to the anteromedial subdomain of the otic anlagen and depends on Fibroblast growth factors (Fgfs) (Abello et al, 2010;Adam et al, 1998;Alsina et al, 2004;Kim et al, 2001;Leger and Brand, 2002;Ma et al, 2000;Millimaki et al, 2007).…”

Fate map of the chicken otic placode

“…However, we cannot rule out other possibilities that have been suggested for DV and AP patterning, in particular the relevance of Shh and retinoic acid signals (Bok et al, 2007(Bok et al, , 2011Brown and Epstein, 2011;Hammond and Whitfield, 2011;Riccomagno et al, 2005;Wu et al, 1998). Restricted spot-like signaling centers from the segmented hindbrain, or even from the pharyngeal endoderm and subjacent mesoderm, might also be involved directly or indirectly in otic placode specification, representing potential sources of additional differential AP signals (Abelló et al, 2010;Alsina et al, 2009;Baker et al, 2008;Begbie et al, 1999;Chen and Streit, 2013;Graham, 2008;Grocott et al, 2012;Ladher et al, 2010;Lleras-Forero and Streit, 2012;McCabe and Bronner-Fraser, 2009;Schlosser, 2006Schlosser, , 2010Schneider-Maunoury and Pujades, 2007;Whitfield and Hammond, 2007).…”

Mechanisms of cranial placode assembly

“…We consider these processes as taking part in the secondary coalescence of placodes, as they start shortly after the end of placodal precursor segregation Stark et al, 1997), and contribute to generate discrete and condensed placodal-derived ganglia by the end of somitogenesis. In the otic placode, another neurogenic placode, neuroblasts also detach from the epithelium to form the statoacoutstic ganglion, but this delamination step affects only a fraction of otic placodal cells (Schneider-Maunoury and Pujades, 2007).…”