Differential expression of α3 and α6 integrins in the developing mouse inner ear

Davies, D. R.; Holley, Matthew C.

doi:10.1002/cne.10161

Cited by 28 publications

(20 citation statements)

References 40 publications

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“…Other cell adhesion molecules may also be responsible for the restriction of cell mixing. For example, differential expression of a3 and a6 integrins in the developing mouse inner ear has been described (Davies and Holley, 2002).…”

Section: Restricted Cell Intermingling Between Otic Proneural and Nonmentioning

confidence: 99%

Early regionalization of the otic placode and its regulation by the Notch signaling pathway

Abelló

Khatri

Giráldez

et al. 2007

Mechanisms of Development

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Otic neuronal precursors are the first cells to be specified and do so in the anterior domain of the otic placode, the proneural domain. In the present study, we have explored the early events of otic proneural regionalization in relation to the activity of the Notch signaling pathway. The proneural domain was characterized by the expression of Sox3, Fgf10 and members of the Notch pathway such as Delta1, Hes5 and Lunatic Fringe. The complementary non-neural domain expressed two patterning genes, Lmx1b and Iroquois1, and the members of the Notch pathway, Serrate1 and Hairy1. Fate map studies and double injections with DiI/DiO showed that labeled cells remained confined to anterior or posterior territories with limited cell intermingling. To explore whether Notch signaling pathway plays a role in the initial regionalization of the otic placode, Notch activity was blocked by a gamma-secretase inhibitor (DAPT). Notch blockade induced the expansion of non-neural genes, Lmx1 and Iroquois1, into the proneural domain. Combined gene expression and DiI experiments showed that these effects were not due to migration of non-neural cells into the proneural domain, suggesting that Notch activity regulates the expression of non-neural genes. This was further confirmed by the electroporation of a dominant-negative form of the Mastermind-like1 gene that caused the up-regulation of Lmx1 within the proneural domain. In addition, Notch pathway was involved in neuronal precursor selection, probably by a classical mechanism of lateral inhibition. We propose that the regionalization of the otic domain into a proneural and a non-neural territory is a very early event in otic development, and that Notch signaling activity is required to exclude the expression of non-neural genes from the proneural territory.

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Section: Restricted Cell Intermingling Between Otic Proneural and Nonmentioning

confidence: 99%

Early regionalization of the otic placode and its regulation by the Notch signaling pathway

Abelló

Khatri

Giráldez

et al. 2007

Mechanisms of Development

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“…Integrins are heterodimeric cell surface receptors consisting of α and β subunits that interact with various extracellular matrix molecules such as laminins, collagens and fibronectin (Reviewed in Kreidberg, 2000). Recently, integrins α6β4 and α3β1 have also been shown to bind Ntn1 (Yebra et al, 2003) and all these subunits are produced in inner ear at some developmental stages (Davies and Holley, 2002).…”

Section: Integrins In the Inner Earmentioning

confidence: 99%

Analysis of Netrin 1 receptors during inner ear development

Matilainen¹,

Haugas²,

Kreidberg³

et al. 2007

Int. J. Dev. Biol.

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Netrin 1 plays key roles in axon guidance and neuronal migration during central nervous system (CNS) development. Outside the CNS, Netrin 1 has been shown to be involved in epithelial morphogenesis of various organs. We have shown that Netrin 1 is essential for inner ear semicircular duct formation, but the involvement of Netrin 1 receptors in this process has remained unknown. Netrin 1 receptors include members of the Deleted in colorectal cancer (Dcc), Unc5-homologue and integrin families. Here we have analysed the expression of these receptor genes during inner ear development and verified the inner ear phenotypes of several receptor mutant mice. Special interest was directed to receptors that could cooperate with Netrin 1 during semicircular duct formation. We show that Neogenin (Neo1), Unc5c as well as integrin β1 (Itgb1) are expressed in periotic mesenchyme, while Dcc, Unc5b, Unc5c, Itga3, Itga6 and Itgb1 are expressed in different parts of the otic epithelium. In spite of the broad and strong expression of several receptors in ear region, none of the analysed receptor mutant embryos showed any defects in inner ear development.

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“…1(a). In the developing otocyst, expression of integrin b4 was restricted to epithelial/mesenchymal borders (Davies and Holley, 2002).…”

Section: Discussionmentioning

confidence: 99%

“…Much remains to be learned about the dynamic expression profiles and functions of integrins in the developing cochlear tissues and sensorineural epithelial cells although the a2 a3, a6, a8, b1, and b4 integrins molecules have been reported (Davies and Holley, 2002). We know that integrins play an essential role in mediating the responses of growth factors such as epidermal growth factor (EGF), fibroblast growth factor (FGF), and platelet-derived growth factor (PDGF).…”

Section: Introductionmentioning

confidence: 98%