The thrombospondin repeat containing protein MIG-21 controls a left–right asymmetric Wnt signaling response in migrating C. elegans neuroblasts

Wnt proteins are secreted signaling molecules that play a central role in development and adult tissue homeostasis. Although several Wnt signal transduction mechanisms have been described in detail, it is still largely unknown how cells are specified to adopt such different Wnt signaling responses....

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Detalhes bibliográficos
Principais autores: Middelkoop, Teije C., Williams, Lisa, Yang, Pei-Tzu, Luchtenberg, Jeroen, Betist, Marco C., Ji, Ni, van Oudenaarden, Alexander, Kenyon, Cynthia, Korswagen, Hendrik C.
Outros Autores: Massachusetts Institute of Technology. Department of Biology
Formato: Artigo
Idioma:en_US
Publicado em: Elsevier 2017
Acesso em linha:http://hdl.handle.net/1721.1/108472
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author Middelkoop, Teije C.
Williams, Lisa
Yang, Pei-Tzu
Luchtenberg, Jeroen
Betist, Marco C.
Ji, Ni
van Oudenaarden, Alexander
Kenyon, Cynthia
Korswagen, Hendrik C.
author2 Massachusetts Institute of Technology. Department of Biology
author_facet Massachusetts Institute of Technology. Department of Biology
Middelkoop, Teije C.
Williams, Lisa
Yang, Pei-Tzu
Luchtenberg, Jeroen
Betist, Marco C.
Ji, Ni
van Oudenaarden, Alexander
Kenyon, Cynthia
Korswagen, Hendrik C.
author_sort Middelkoop, Teije C.
collection MIT
description Wnt proteins are secreted signaling molecules that play a central role in development and adult tissue homeostasis. Although several Wnt signal transduction mechanisms have been described in detail, it is still largely unknown how cells are specified to adopt such different Wnt signaling responses. Here, we have used the stereotypic migration of the C. elegans Q neuroblasts as a model to study how two initially equivalent cells are instructed to activate either β-catenin dependent or independent Wnt signaling pathways to control the migration of their descendants along the anteroposterior axis. We find that the specification of this difference in Wnt signaling response is dependent on the thrombospondin repeat containing protein MIG-21, which acts together with the netrin receptor UNC-40/DCC to control an initial left–right asymmetric polarization of the Q neuroblasts. Furthermore, we show that the direction of this polarization determines the threshold for Wnt/β-catenin signaling, with posterior polarization sensitizing for activation of this pathway. We conclude that MIG-21 and UNC-40 control the asymmetry in Wnt signaling response by restricting posterior polarization to one of the two Q neuroblasts.
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spelling mit-1721.1/1084722022-10-01T23:46:57Z The thrombospondin repeat containing protein MIG-21 controls a left–right asymmetric Wnt signaling response in migrating C. elegans neuroblasts Middelkoop, Teije C. Williams, Lisa Yang, Pei-Tzu Luchtenberg, Jeroen Betist, Marco C. Ji, Ni van Oudenaarden, Alexander Kenyon, Cynthia Korswagen, Hendrik C. Massachusetts Institute of Technology. Department of Biology Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Massachusetts Institute of Technology. Department of Physics van Oudenaarden, Alexander van Oudenaarden, Alexander Ji, Ni Wnt proteins are secreted signaling molecules that play a central role in development and adult tissue homeostasis. Although several Wnt signal transduction mechanisms have been described in detail, it is still largely unknown how cells are specified to adopt such different Wnt signaling responses. Here, we have used the stereotypic migration of the C. elegans Q neuroblasts as a model to study how two initially equivalent cells are instructed to activate either β-catenin dependent or independent Wnt signaling pathways to control the migration of their descendants along the anteroposterior axis. We find that the specification of this difference in Wnt signaling response is dependent on the thrombospondin repeat containing protein MIG-21, which acts together with the netrin receptor UNC-40/DCC to control an initial left–right asymmetric polarization of the Q neuroblasts. Furthermore, we show that the direction of this polarization determines the threshold for Wnt/β-catenin signaling, with posterior polarization sensitizing for activation of this pathway. We conclude that MIG-21 and UNC-40 control the asymmetry in Wnt signaling response by restricting posterior polarization to one of the two Q neuroblasts. 2017-04-27T20:20:16Z 2017-04-27T20:20:16Z 2012-01 Article http://purl.org/eprint/type/JournalArticle 0012-1606 1095-564X http://hdl.handle.net/1721.1/108472 Middelkoop, Teije C., Lisa Williams, Pei-Tzu Yang, Jeroen Luchtenberg, Marco C. Betist, Ni Ji, Alexander van Oudenaarden, Cynthia Kenyon, and Hendrik C. Korswagen. “The Thrombospondin Repeat Containing Protein MIG-21 Controls a Left–right Asymmetric Wnt Signaling Response in Migrating C. Elegans Neuroblasts.” Developmental Biology 361, no. 2 (January 2012): 338–348. en_US http://dx.doi.org/10.1016/j.ydbio.2011.10.029 Developmental Biology Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier Prof. van Oudenaarden via Mat Willmott
spellingShingle Middelkoop, Teije C.
Williams, Lisa
Yang, Pei-Tzu
Luchtenberg, Jeroen
Betist, Marco C.
Ji, Ni
van Oudenaarden, Alexander
Kenyon, Cynthia
Korswagen, Hendrik C.
The thrombospondin repeat containing protein MIG-21 controls a left–right asymmetric Wnt signaling response in migrating C. elegans neuroblasts
title The thrombospondin repeat containing protein MIG-21 controls a left–right asymmetric Wnt signaling response in migrating C. elegans neuroblasts
title_full The thrombospondin repeat containing protein MIG-21 controls a left–right asymmetric Wnt signaling response in migrating C. elegans neuroblasts
title_fullStr The thrombospondin repeat containing protein MIG-21 controls a left–right asymmetric Wnt signaling response in migrating C. elegans neuroblasts
title_full_unstemmed The thrombospondin repeat containing protein MIG-21 controls a left–right asymmetric Wnt signaling response in migrating C. elegans neuroblasts
title_short The thrombospondin repeat containing protein MIG-21 controls a left–right asymmetric Wnt signaling response in migrating C. elegans neuroblasts
title_sort thrombospondin repeat containing protein mig 21 controls a left right asymmetric wnt signaling response in migrating c elegans neuroblasts
url http://hdl.handle.net/1721.1/108472
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