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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

Canonical and non-canonical Wnt signaling pathways. The Wnt pathway can be classified broadly as canonical and non-canonical. Both pathways are activated by a Wnt ligand to the Frizzled receptor. The active canonical pathway is mediated by β-catenin, which translocates into the nucleus and it acts as a co-activator of the TCF/LEF transcription factor, leading to the upregulation of Wnt target genes. The two major non-canonical pathways are Wnt/calcium and Planar Cell Polarity (PCP) pathways. In the Wnt/calcium pathway, Wnt binding to Frizzled activates Dvl, which stimulates calcium release from the endoplasmic reticulum, activating calcium-binding proteins including protein kinase C (PKC) and calmodulin-dependent kinase II (CamKII), and in turn, the transcription factor NFAT. The Wnt/calcium pathway has been shown to regulate cell movement and axis formation during embryogenesis. The Wnt/PCP pathway is mediated by the GTPases RhoA and Ras, which, via the activation of the RhoA-Rho-associated kinase (ROCK) axis or JNK, can exert effects on the cytoskeleton.
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Figure 3: Canonical and non-canonical Wnt signaling pathways. The Wnt pathway can be classified broadly as canonical and non-canonical. Both pathways are activated by a Wnt ligand to the Frizzled receptor. The active canonical pathway is mediated by β-catenin, which translocates into the nucleus and it acts as a co-activator of the TCF/LEF transcription factor, leading to the upregulation of Wnt target genes. The two major non-canonical pathways are Wnt/calcium and Planar Cell Polarity (PCP) pathways. In the Wnt/calcium pathway, Wnt binding to Frizzled activates Dvl, which stimulates calcium release from the endoplasmic reticulum, activating calcium-binding proteins including protein kinase C (PKC) and calmodulin-dependent kinase II (CamKII), and in turn, the transcription factor NFAT. The Wnt/calcium pathway has been shown to regulate cell movement and axis formation during embryogenesis. The Wnt/PCP pathway is mediated by the GTPases RhoA and Ras, which, via the activation of the RhoA-Rho-associated kinase (ROCK) axis or JNK, can exert effects on the cytoskeleton.

Mentions: In addition to canonical Wnt signaling, Wnt proteins can exert cellular responses in a β-catenin-independent manner via two separate non-canonical pathways (Figure 3). First, the planar-cell-polarity (PCP) pathway signals through Frizzled receptors and Disheveled to primarily rearrange the cytoskeleton, change cell morphology, and affect gene expression. Secondly, the Wnt/calcium pathway signals through phospholipase C to release intracellular calcium stores to ultimately affect genes involved in migration and cell fate (Gómez-Orte et al., 2013).


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

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

Canonical and non-canonical Wnt signaling pathways. The Wnt pathway can be classified broadly as canonical and non-canonical. Both pathways are activated by a Wnt ligand to the Frizzled receptor. The active canonical pathway is mediated by β-catenin, which translocates into the nucleus and it acts as a co-activator of the TCF/LEF transcription factor, leading to the upregulation of Wnt target genes. The two major non-canonical pathways are Wnt/calcium and Planar Cell Polarity (PCP) pathways. In the Wnt/calcium pathway, Wnt binding to Frizzled activates Dvl, which stimulates calcium release from the endoplasmic reticulum, activating calcium-binding proteins including protein kinase C (PKC) and calmodulin-dependent kinase II (CamKII), and in turn, the transcription factor NFAT. The Wnt/calcium pathway has been shown to regulate cell movement and axis formation during embryogenesis. The Wnt/PCP pathway is mediated by the GTPases RhoA and Ras, which, via the activation of the RhoA-Rho-associated kinase (ROCK) axis or JNK, can exert effects on the cytoskeleton.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Canonical and non-canonical Wnt signaling pathways. The Wnt pathway can be classified broadly as canonical and non-canonical. Both pathways are activated by a Wnt ligand to the Frizzled receptor. The active canonical pathway is mediated by β-catenin, which translocates into the nucleus and it acts as a co-activator of the TCF/LEF transcription factor, leading to the upregulation of Wnt target genes. The two major non-canonical pathways are Wnt/calcium and Planar Cell Polarity (PCP) pathways. In the Wnt/calcium pathway, Wnt binding to Frizzled activates Dvl, which stimulates calcium release from the endoplasmic reticulum, activating calcium-binding proteins including protein kinase C (PKC) and calmodulin-dependent kinase II (CamKII), and in turn, the transcription factor NFAT. The Wnt/calcium pathway has been shown to regulate cell movement and axis formation during embryogenesis. The Wnt/PCP pathway is mediated by the GTPases RhoA and Ras, which, via the activation of the RhoA-Rho-associated kinase (ROCK) axis or JNK, can exert effects on the cytoskeleton.
Mentions: In addition to canonical Wnt signaling, Wnt proteins can exert cellular responses in a β-catenin-independent manner via two separate non-canonical pathways (Figure 3). First, the planar-cell-polarity (PCP) pathway signals through Frizzled receptors and Disheveled to primarily rearrange the cytoskeleton, change cell morphology, and affect gene expression. Secondly, the Wnt/calcium pathway signals through phospholipase C to release intracellular calcium stores to ultimately affect genes involved in migration and cell fate (Gómez-Orte et al., 2013).

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