Distinct expression patterns of notch family receptors and ligands during development of the mammalian inner ear

Abstract

The cochlea and vestibular structures of the inner ear labyrinth develop from the otic capsule via step-wise regional and cell fate specification. Each inner ear structure contains a sensory epithelium, composed of hair cells, the mechanosensory transducers, and supporting cells. We examined the spatio-temporal expression of genes in the Notch signaling pathway, Notch receptors (Notch1-4) and two ligands, Jagged1 and Delta1, in the developing mammalian inner ear. Our results show that Notch1 and Jagged1 are first expressed in the otic vesicle, likely involved in differentiation of the VIIIth nerve ganglion neurons, and subsequently within the inner ear sensory epithelia, temporally coincident with initial hair cell differentiation. Notch1 expression is specific to hair cells and Jagged1 to supporting cells. Their expression persists into adult. Notch2, Notch3, Notch4, and Delta1 are excluded from the inner ear epithelia. These data support the hypothesis that Notch signaling is involved in hair cell differentiation during inner ear morphogenesis.

Acheate‐scute like 1 (Ascl1) is required for normal delta‐like (Dll) gene expression and notch signaling during retinal development

“…We used a mouse Notch1 14.3Kb promoter construct driving GFP to identify Notch1 expressing progenitor cells (Notch1GFP; Lewis et al, 1998), a mouse Hes5 0.76Kb promoter driving destabilized GFP to identify Hes5 and active Notch signaling in progenitor cells (Hes5d2GFP, Takebayashi et al, 1995;Ohtsuka et al, 2006;Nelson et al, 2006), and a mouse Dll1 4.3Kb promoter construct driving LacZ to identify Dll1 expressing progenitor cells (Dll1LacZ; Beckers et al, 2000;Castro et al, 2006). We also created a Dll3 reporter construct, since Ascl1 loss of function especially affected Dll3 expression.…”

Molecular Genetics of Vestibular Organ Development

“…Based on expression studies of Notch signaling molecules, it has been proposed that the expression of Notch ligands, Delta and Jagged/Serrate, on the surface of presumptive sensory hair cells activated Notch receptors present on neighboring cells (Adam et al 1998;Lewis et al 1998). This activation of Notch receptors in the neighboring cells induced them to develop into supporting cells.…”

“…Then, these neuroblasts migrate away and undergo further proliferation before coalescing to form a ganglion that later divides to form the vestibular and spiral ganglia (Carney and Couve 1989). The Notch signaling pathway is important for the neuroblast determination, as indicated by the expression of Delta1, Jagged1, and L-fng in the neurogenic domain of the otic cup and otocyst (Adam et al 1998;Lewis et al 1998;Morsli et al 1998). In addition, the number of vestibulocochlear neurons is increased in the zebrafish (B.rerio) mind bomb mutant in which the Notch signaling pathway is postulated to be affected (Haddon et al 1998).…”

Basic helix–loop–helix gene Hes6 delineates the sensory hair cell lineage in the inner ear

“…The molecular mechanisms underlying the development of the sensory lineage and the patterning of the or-gan of Corti have been studied extensively (Adam et al, 1998;Haddon et al, 1998;Lewis et al, 1998;Lewis, 1998;Bermingham et al, 1999;Lanford et al, 1999Lanford et al, , 2000Morrison et al, 1999;Riley et al, 1999;Eddison et al, 2000;Zhang et al, 2000;Zine et al, 2000Zine et al, , 2001Tsai et al, 2001;Bryant et al, 2002;Chen et al, 2002;Fekete and Wu, 2002;Radde-Gallwitz et al, 2004;Woods et al, 2004;Daudet and Lewis, 2005;Kiernan et al, 2005a,b;Matei et al, 2005). In particular, two classes of basic helix-loop-helix (bHLH)-containing factors, namely the positively and negatively acting transcription factors, have been shown to play essential roles in the differentiation of sensory hair cells and the patterning of the sensory mosaic in the organ of Corti (Bermingham et al, 1999;Zine et al, 2000Zine et al, , 2001Chen et al, 2002;Woods et al, 2004).…”

“…Together, these data suggest that Hes1 and Hes5 play an anti-neurogenic role for hair cell differentiation. It is hypothesized that Hes1 and Hes5 act downstream of activated Notch pathway (Jarriault et al, 1995;Chen et al, 1997;Lewis, 1998;Ohtsuka et al, 1999;Zine et al, 2001) to prevent the cells surrounding the hair cells from differentiating into the same cell type (Adam et al, 1998;Haddon et al, 1998;Lewis et al, 1998;Lanford et al, 1999;Morrison et al, 1999;Riley et al, 1999;Eddison et al, 2000;Zine et al, 2000;Zhang et al, 2000;Kiernan et al, 2001;Tsai et al, 2001;Kiernan et al, 2005b) and to restrict the boundary of the sensory epithelium (Daudet and Lewis, 2005).…”