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Notch signaling augments the canonical Wnt pathway to specify the size of the otic placode

Jayasena, Chathurani S. and Ohyama, Takahiro and Segil, Neil and Groves, Andrew K. (2008) Notch signaling augments the canonical Wnt pathway to specify the size of the otic placode. Development, 135 (13). pp. 2251-2261. ISSN 0950-1991.

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The inner ear derives from a patch of ectoderm defined by expression of the transcription factor Pax2. We recently showed that this Pax2^+ ectoderm gives rise not only to the otic placode but also to the surrounding cranial epidermis, and that Wnt signaling mediates this placode-epidermis fate decision. We now present evidence for reciprocal interactions between the Wnt and Notch signaling pathways during inner ear induction. Activation of Notch1 in Pax2+ ectoderm expands the placodal epithelium at the expense of cranial epidermis, whereas loss of Notch1 leads to a reduction in the size of the otic placode. We show that Wnt signaling positively regulates Notch pathway genes such as Jag1, Notch1 and Hes1, and we have used transgenic Wnt reporter mice to show that Notch signaling can modulate the canonical Wnt pathway. Gain- and loss-of-function mutations in the Notch and Wnt pathways reveal that some aspects of otic placode development - such as Pax8 expression and the morphological thickening of the placode - can be regulated independently by either Notch or Wnt signals. Our results suggest that Wnt signaling specifies the size of the otic placode in two ways, by directly upregulating a subset of otic genes, and by positively regulating components of the Notch signaling pathway, which then act to augment Wnt signaling.

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Additional Information:© 2008. Accepted 12 May 2008.First published online 21 May 2008. We thank the following colleagues for generously providing transgenic mice for this study: Charles Murtaugh (N1ICD mice), Daniel Dufort (Wnt reporter mice), Ron Conlon (Notch1 mutant mice), Tasuku Honjo (conditional Rbpj mice) and Mark Taketo (cAct β-catenin mice). We also thank Jeffrey Nye, Achim Gossler, Tim Mitsiadu, Ryoichiro Kageyama, Thomas Vogt and Andy McMahon for gifts of probes; Juan Llamas, Welly Makmura, Sheri Juntilla, Francesca Della Ripa and Juemei Wang for excellent technical support; and for Groves and Segil lab members for help and advice during this project. This work was funded by the House Ear Institute, by a March of Dimes Research Grant (A.K.G.), and by RO1DC04675 (A.K.G.) and RO1DC06185 (A.K.G. and N.S.).
Funding AgencyGrant Number
House Ear InstituteUNSPECIFIED
March of Dimes Research Grant (A.K.G.)RO1DC04675
(A.K.G. and N.S.)RO1DC06185
Subject Keywords:Mouse, Otic placode, Wnt, β-Catenin, Notch1, Jagged 1, Inner ear
Issue or Number:13
Record Number:CaltechAUTHORS:20090410-110421894
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:13926
Deposited By: Ruth Sustaita
Deposited On:14 Jul 2009 20:46
Last Modified:03 Oct 2019 00:45

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