From placode to polarization: new tunes in inner ear development

Barald, Kate F.; Kelley, Matthew W.

doi:10.1242/dev.01339

Cited by 213 publications

(183 citation statements)

References 114 publications

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“…More than 100 loci have been mapped that can lead to non-syndromic hearing loss (Friedman and Griffith, 2003). In addition to components of the auditory transduction pathway, some of these mutations lie in critical transcription factors that regulate inner ear embryonic development including BRN3C, ATOH1, SOX2, NGN1 and GFI1 (reviewed in: Barald and Kelley, 2004;Housley et al, 2006).…”

Section: Resultsmentioning

confidence: 99%

Expression of LHX3 and SOX2 during mouse inner ear development

Hume

Bratt

Oesterle

2007

Gene Expression Patterns

138

140

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A cascade of transcription factors is believed to regulate the coordinate differentiation of primordial inner ear cells into the subtypes of hair cells and supporting cells. While candidate genes involved in this process have been identified, the temporal and spatial patterns of expression of many of these have not been carefully described during the extended period of inner ear development and functional maturation. We systematically examined the expression of two such transcription factors, LHX3 and SOX2, from the time of hair cell terminal mitoses into adulthood. We show that LHX3 is expressed specifically in auditory and vestibular hair cells soon after terminal mitoses and persists into the adult in vestibular hair cells. While SOX2 expression is widespread in the inner ear sensory epithelia prior to hair cell differentiation, it has a unique pattern of expression in the mature auditory and vestibular organs.

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Section: Resultsmentioning

confidence: 99%

Expression of LHX3 and SOX2 during mouse inner ear development

Hume

Bratt

Oesterle

2007

Gene Expression Patterns

138

140

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“…IMO2B1-conditioned medium promoted outgrowth of SAG explants and also promoted outgrowth and survival of dissociated SAG neurons similar to that observed with chick or mouse ODF. It is important to note that the cells of the IMO2B1 line maintain many of the characteristics of developing inner ear sensory epithelia (Gerlach et al 2000;Thompson et al 2003;Germiller et al 2004;Barald and Kelley 2004). It is believed that the IMO2B1 cell line represents a multipotential precursor population that can give rise either to HC-like or SC-like cells under the influence of specific culture conditions (Germiller et al 2004).…”

Section: Discussionmentioning

confidence: 99%

“…Target-derived growth and survival factors are critically important for the development of neuronal populations. Such factors also appear to regulate innervation of the developing inner ear at the otocyst stage (reviewed by Barald and Kelley 2004). During early stages of embryogenesis [embryonic day (E) 4-6 chick; E11-14 mouse, rat], the otocyst releases (a) soluble factor(s) that promote the outgrowth and survival of innervating statoacoustic ganglion (SAG) neurons (Ard and Morest 1984;Ard et al 1985;Lefebvre et al 1990;Bianchi andCohan 1991, 1993a).…”

Section: Introductionmentioning

confidence: 99%

Immortalized Mouse Inner Ear Cell Lines Demonstrate a Role for Chemokines in Promoting the Growth of Developing Statoacoustic Ganglion Neurons

Bianchi

Daruwalla

Roth

et al. 2005

JARO

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The target-derived factors necessary for promoting initial outgrowth from the statoacoustic ganglion (SAG) to the inner ear have not been fully characterized. In the present study, conditioned medium from embryonic Immortomouse inner ear cell lines that maintain many characteristics of developing inner ear sensory epithelia were screened for neurite-promoting activity. Conditioned medium found to be positive for promoting SAG neurite outgrowth and neuronal survival was then tested for the presence of chemokines, molecules that have not previously been investigated for promoting SAG outgrowth. One candidate molecule, monocyte chemotactic protein 1 (MCP-1), was detected in the conditioned medium and subsequently localized to mouse hair cells by immunocytochemistry. In vitro studies demonstrated that function-blocking MCP-1 antibodies decreased the amount of SAG neurite outgrowth induced by the conditioned medium and that subsequent addition of MCP-1 protein was able to promote outgrowth when added to the antibodytreated conditioned medium. The use of the Immortomouse cell lines proved valuable in identifying this candidate cofactor that promotes outgrowth of earlystage SAG nerve fibers and is expressed in embryonic hair cells.

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“…Remarkably, stereocilia show an apparently stable and regularly graded increase in length from row to row within the stereociliary bundle, even though their PAB appears to undergo actin treadmilling, at least in transfected hair cells in cultured cochlear explants [19]. To signal properly the stereociliary staircase on each hair cell must adopt a specific orientation relative to anatomical landmarks within the cochlea or vestibular system, a feat accomplished in part through the planar cell polarity pathway [20,21]. The overall length of the stereociliary bundle, commonly scored by measuring the length of the tallest stereocilia within a bundle, varies in a reproducible way according to hair cell type or position.…”

Section: Espins In Hair Cell Stereociliamentioning

confidence: 99%

Espins and the actin cytoskeleton of hair cell stereocilia and sensory cell microvilli

Sekerková

Zheng

Loomis

et al. 2006

Cell. Mol. Life Sci.

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The espins are novel actin-bundling proteins that are produced in multiple isoforms from a single gene. They are present at high concentration in the parallel actin bundle of hair cell stereocilia and are the target of deafness mutations in mice and humans. Espins are also enriched in the microvilli of taste receptor cells, solitary chemoreceptor cells, vomeronasal sensory neurons and Merkel cells, suggesting that espins play important roles in the microvillar projections of vertebrate sensory cells. Espins are potent actin-bundling proteins that are not inhibited by Ca 2+ . In cells, they efficiently elongate parallel actin bundles and, thereby, help determine the steady-state length of microvilli and stereocilia. Espins bind actin monomer via their WH2 domain and can assemble actin bundles in cells. Certain espin isoforms can also bind phosphatidylinositol 4,5-bisphosphate, profilins or SH3 proteins. These biological activities distinguish espins from other actin-bundling proteins and may make them well-suited to sensory cells. KeywordsEspin; actin; hair cell; stereocilia; microvilli; sensory; deafness; taste The stereocilia and microvilli of vertebrate sensory cells and their actinbundling proteinsMany classes of vertebrate sensory cells detect chemical or mechanical stimuli through microvilli or their derivatives, such as stereocilia. These relatively long-lived, fingerlike specializations of the plasma membrane are built around a common cytoskeletal element -the parallel actin bundle (PAB) [1]. PABs consist of tightly packed collections of actin filaments cross-linked by actin-bundling proteins. The filaments are aligned along their longitudinal axis and display a uniform polarity with respect to their preferred ends for actin monomer addition, which in microvilli and stereocilia is positioned at the distal tip. The PAB displays hallmarks of a supramolecular scaffold that determines the placement, dimensions, flexibility and signaling properties of microvilli and stereocilia. Although filopodia also contain a PAB at their core and are believed to sense the local environment, they are considerably more dynamic and differ significantly from microvilli and stereocilia in their molecular composition and biogenesis [2].

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From placode to polarization: new tunes in inner ear development

Cited by 213 publications

References 114 publications

Expression of LHX3 and SOX2 during mouse inner ear development

Expression of LHX3 and SOX2 during mouse inner ear development

Immortalized Mouse Inner Ear Cell Lines Demonstrate a Role for Chemokines in Promoting the Growth of Developing Statoacoustic Ganglion Neurons

Espins and the actin cytoskeleton of hair cell stereocilia and sensory cell microvilli

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