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Making sense of Wnt signaling-linking hair cell regeneration to development.

Jansson L, Kim GS, Cheng AG - Front Cell Neurosci (2015)

Bottom Line: The complexity of the pathway can be attributed to the myriad of Wnt and Frizzled combinations as well as its diverse context-dependent functions.In regenerating sensory organs from non-mammalian species, Wnt signaling can also regulate the extent of proliferative hair cell regeneration.We also discuss possible future directions and the potential application and limitation of Wnt signaling in augmenting hair cell regeneration.

View Article: PubMed Central - PubMed

Affiliation: Department of Otolaryngology-Head and Neck Surgery, School of Medicine, Stanford University Stanford, CA, USA.

ABSTRACT
Wnt signaling is a highly conserved pathway crucial for development and homeostasis of multicellular organisms. Secreted Wnt ligands bind Frizzled receptors to regulate diverse processes such as axis patterning, cell division, and cell fate specification. They also serve to govern self-renewal of somatic stem cells in several adult tissues. The complexity of the pathway can be attributed to the myriad of Wnt and Frizzled combinations as well as its diverse context-dependent functions. In the developing mouse inner ear, Wnt signaling plays diverse roles, including specification of the otic placode and patterning of the otic vesicle. At later stages, its activity governs sensory hair cell specification, cell cycle regulation, and hair cell orientation. In regenerating sensory organs from non-mammalian species, Wnt signaling can also regulate the extent of proliferative hair cell regeneration. This review describes the current knowledge of the roles of Wnt signaling and Wnt-responsive cells in hair cell development and regeneration. We also discuss possible future directions and the potential application and limitation of Wnt signaling in augmenting hair cell regeneration.

No MeSH data available.


Related in: MedlinePlus

Wnt expression in developing inner ear in chicken and mice. Overview of Wnt gene expression in the developing inner ear (Riccomagno et al., 2005; Noda et al., 2012; Vendrell et al., 2013). Dark shaded columns on the left represent epithelium of otic cyst and lighter shaded columns on the right periotic mesenchymal tissues. In later developmental states, dark shaded columns on the left represent pro-sensory and sensory areas whereas lighter shaded columns on the right represent non-sensory areas (Dabdoub et al., 2003; Wang et al., 2005; Qian et al., 2007; Etheridge et al., 2008; Sienknecht and Fekete, 2008, 2009; Rida and Chen, 2009; Chai et al., 2011; Bohnenpoll et al., 2014). *determined by PCR, specific cell type expression unknown.
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Figure 2: Wnt expression in developing inner ear in chicken and mice. Overview of Wnt gene expression in the developing inner ear (Riccomagno et al., 2005; Noda et al., 2012; Vendrell et al., 2013). Dark shaded columns on the left represent epithelium of otic cyst and lighter shaded columns on the right periotic mesenchymal tissues. In later developmental states, dark shaded columns on the left represent pro-sensory and sensory areas whereas lighter shaded columns on the right represent non-sensory areas (Dabdoub et al., 2003; Wang et al., 2005; Qian et al., 2007; Etheridge et al., 2008; Sienknecht and Fekete, 2008, 2009; Rida and Chen, 2009; Chai et al., 2011; Bohnenpoll et al., 2014). *determined by PCR, specific cell type expression unknown.

Mentions: Initial work on the developing chicken otic placode implicated the involvement of Wnt8c (mouse Wnt8a) in otic ectoderm specification (Ladher et al., 2000; Urness et al., 2010). However, deletion of Wnt8c in the developing otic placode in zebrafish only delayed, but did not prevent, otic placode development (Phillips et al., 2004). Redundancy among Wnt ligands is well established in numerous developing systems and mapping of gene expression show that most components of the pathway, including the Wnt ligands, are expressed in a strict spatio-temporal manner during chicken inner ear development (Sienknecht and Fekete, 2009; Figure 2) suggesting that the partial overlap in expression of Wnts may account for such redundancy (Logan and Nusse, 2004; Gleason et al., 2006; Sienknecht and Fekete, 2009). For example, although individual gene deletions of Wnt1 or Wnt8a result in normal inner ear development, mice deficient in both Wnt1 and Wnt8a exhibit disruption of the dorsal patterning of the otocyst. This results in an underdeveloped endolymphatic sac while the formation of the otic placode and cochlear and vestibular sensory organs are unaffected (Vendrell et al., 2013). In addition, Wnt1 and Wnt3a have been shown to work redundantly in regulating the patterning of the dorsal otocyst. Riccomagno et al. determined that although the placode develops normally in Wnt1−/−; Wnt3a−/− double knockout mice, absence of these Wnt members from the dorsal neural tube during later stages of otocyst development results in severe vestibular defects, including a complete lack of utricle and saccule. Intriguingly, in addition to the dorsal vestibular defects, the double mutant also displays a ventral phenotype with a hypoplastic cochlea (Riccomagno et al., 2005). The authors also found that Wnt signaling is both sufficient and necessary for inducing the expression of dorsal otic genes (Dlx5, Gbx2). Lastly, Wnt-responsive cells in the early otic epithelium was found to contribute to several different parts of the inner ear, including the majority of the vestibular system and parts of the cochlea. A similar finding on the effect of Wnt3a in dorsal-ventral patterning of the inner ear was recently described in the zebrafish (Forristall et al., 2014).


Making sense of Wnt signaling-linking hair cell regeneration to development.

Jansson L, Kim GS, Cheng AG - Front Cell Neurosci (2015)

Wnt expression in developing inner ear in chicken and mice. Overview of Wnt gene expression in the developing inner ear (Riccomagno et al., 2005; Noda et al., 2012; Vendrell et al., 2013). Dark shaded columns on the left represent epithelium of otic cyst and lighter shaded columns on the right periotic mesenchymal tissues. In later developmental states, dark shaded columns on the left represent pro-sensory and sensory areas whereas lighter shaded columns on the right represent non-sensory areas (Dabdoub et al., 2003; Wang et al., 2005; Qian et al., 2007; Etheridge et al., 2008; Sienknecht and Fekete, 2008, 2009; Rida and Chen, 2009; Chai et al., 2011; Bohnenpoll et al., 2014). *determined by PCR, specific cell type expression unknown.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4356074&req=5

Figure 2: Wnt expression in developing inner ear in chicken and mice. Overview of Wnt gene expression in the developing inner ear (Riccomagno et al., 2005; Noda et al., 2012; Vendrell et al., 2013). Dark shaded columns on the left represent epithelium of otic cyst and lighter shaded columns on the right periotic mesenchymal tissues. In later developmental states, dark shaded columns on the left represent pro-sensory and sensory areas whereas lighter shaded columns on the right represent non-sensory areas (Dabdoub et al., 2003; Wang et al., 2005; Qian et al., 2007; Etheridge et al., 2008; Sienknecht and Fekete, 2008, 2009; Rida and Chen, 2009; Chai et al., 2011; Bohnenpoll et al., 2014). *determined by PCR, specific cell type expression unknown.
Mentions: Initial work on the developing chicken otic placode implicated the involvement of Wnt8c (mouse Wnt8a) in otic ectoderm specification (Ladher et al., 2000; Urness et al., 2010). However, deletion of Wnt8c in the developing otic placode in zebrafish only delayed, but did not prevent, otic placode development (Phillips et al., 2004). Redundancy among Wnt ligands is well established in numerous developing systems and mapping of gene expression show that most components of the pathway, including the Wnt ligands, are expressed in a strict spatio-temporal manner during chicken inner ear development (Sienknecht and Fekete, 2009; Figure 2) suggesting that the partial overlap in expression of Wnts may account for such redundancy (Logan and Nusse, 2004; Gleason et al., 2006; Sienknecht and Fekete, 2009). For example, although individual gene deletions of Wnt1 or Wnt8a result in normal inner ear development, mice deficient in both Wnt1 and Wnt8a exhibit disruption of the dorsal patterning of the otocyst. This results in an underdeveloped endolymphatic sac while the formation of the otic placode and cochlear and vestibular sensory organs are unaffected (Vendrell et al., 2013). In addition, Wnt1 and Wnt3a have been shown to work redundantly in regulating the patterning of the dorsal otocyst. Riccomagno et al. determined that although the placode develops normally in Wnt1−/−; Wnt3a−/− double knockout mice, absence of these Wnt members from the dorsal neural tube during later stages of otocyst development results in severe vestibular defects, including a complete lack of utricle and saccule. Intriguingly, in addition to the dorsal vestibular defects, the double mutant also displays a ventral phenotype with a hypoplastic cochlea (Riccomagno et al., 2005). The authors also found that Wnt signaling is both sufficient and necessary for inducing the expression of dorsal otic genes (Dlx5, Gbx2). Lastly, Wnt-responsive cells in the early otic epithelium was found to contribute to several different parts of the inner ear, including the majority of the vestibular system and parts of the cochlea. A similar finding on the effect of Wnt3a in dorsal-ventral patterning of the inner ear was recently described in the zebrafish (Forristall et al., 2014).

Bottom Line: The complexity of the pathway can be attributed to the myriad of Wnt and Frizzled combinations as well as its diverse context-dependent functions.In regenerating sensory organs from non-mammalian species, Wnt signaling can also regulate the extent of proliferative hair cell regeneration.We also discuss possible future directions and the potential application and limitation of Wnt signaling in augmenting hair cell regeneration.

View Article: PubMed Central - PubMed

Affiliation: Department of Otolaryngology-Head and Neck Surgery, School of Medicine, Stanford University Stanford, CA, USA.

ABSTRACT
Wnt signaling is a highly conserved pathway crucial for development and homeostasis of multicellular organisms. Secreted Wnt ligands bind Frizzled receptors to regulate diverse processes such as axis patterning, cell division, and cell fate specification. They also serve to govern self-renewal of somatic stem cells in several adult tissues. The complexity of the pathway can be attributed to the myriad of Wnt and Frizzled combinations as well as its diverse context-dependent functions. In the developing mouse inner ear, Wnt signaling plays diverse roles, including specification of the otic placode and patterning of the otic vesicle. At later stages, its activity governs sensory hair cell specification, cell cycle regulation, and hair cell orientation. In regenerating sensory organs from non-mammalian species, Wnt signaling can also regulate the extent of proliferative hair cell regeneration. This review describes the current knowledge of the roles of Wnt signaling and Wnt-responsive cells in hair cell development and regeneration. We also discuss possible future directions and the potential application and limitation of Wnt signaling in augmenting hair cell regeneration.

No MeSH data available.


Related in: MedlinePlus