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Proteoglycan interactions with Sonic Hedgehog specify mitogenic responses

Sonic Hedgehog (Shh) has dual roles in vertebrate development, as it promotes progenitor cell proliferation and induces tissue patterning. Here we show mitogenic and patterning functions of Shh can be uncoupled from one another. Using a genetic approach to selectively inhibit Shh-proteoglycan intera...

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Autores principales: Chan, Jennifer A., Balasubramanian, Srividya, Witt, Rochelle M., Nazemi, Kellie J., Choi, Yoojin, Pazyra-Murphy, Maria F., Walsh, Carolyn O., Thompson, Margaret, Segal, Rosalind A.
Formato: Texto
Lenguaje:English
Publicado: 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2676236/
https://www.ncbi.nlm.nih.gov/pubmed/19287388
http://dx.doi.org/10.1038/nn.2287
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author Chan, Jennifer A.
Balasubramanian, Srividya
Witt, Rochelle M.
Nazemi, Kellie J.
Choi, Yoojin
Pazyra-Murphy, Maria F.
Walsh, Carolyn O.
Thompson, Margaret
Segal, Rosalind A.
author_facet Chan, Jennifer A.
Balasubramanian, Srividya
Witt, Rochelle M.
Nazemi, Kellie J.
Choi, Yoojin
Pazyra-Murphy, Maria F.
Walsh, Carolyn O.
Thompson, Margaret
Segal, Rosalind A.
author_sort Chan, Jennifer A.
collection PubMed
description Sonic Hedgehog (Shh) has dual roles in vertebrate development, as it promotes progenitor cell proliferation and induces tissue patterning. Here we show mitogenic and patterning functions of Shh can be uncoupled from one another. Using a genetic approach to selectively inhibit Shh-proteoglycan interactions in a mouse model, we show binding of Shh to proteoglycans is required for proliferation of neural stem/precursor cells but not for tissue patterning. Shh-proteoglycan interactions regulate both spatial and temporal features of Shh signaling. Proteoglycans localize Shh to specialized mitogenic niches and also act at the single cell level to regulate the duration of Shh signaling, thereby promoting a gene expression program important for cell division. As activation of the Shh pathway is a feature of diverse human cancers, selective stimulation of proliferation by Shh-proteoglycan interactions may also figure prominently in neoplastic growth.
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spelling pubmed-26762362009-10-01 Proteoglycan interactions with Sonic Hedgehog specify mitogenic responses Chan, Jennifer A. Balasubramanian, Srividya Witt, Rochelle M. Nazemi, Kellie J. Choi, Yoojin Pazyra-Murphy, Maria F. Walsh, Carolyn O. Thompson, Margaret Segal, Rosalind A. Nat Neurosci Article Sonic Hedgehog (Shh) has dual roles in vertebrate development, as it promotes progenitor cell proliferation and induces tissue patterning. Here we show mitogenic and patterning functions of Shh can be uncoupled from one another. Using a genetic approach to selectively inhibit Shh-proteoglycan interactions in a mouse model, we show binding of Shh to proteoglycans is required for proliferation of neural stem/precursor cells but not for tissue patterning. Shh-proteoglycan interactions regulate both spatial and temporal features of Shh signaling. Proteoglycans localize Shh to specialized mitogenic niches and also act at the single cell level to regulate the duration of Shh signaling, thereby promoting a gene expression program important for cell division. As activation of the Shh pathway is a feature of diverse human cancers, selective stimulation of proliferation by Shh-proteoglycan interactions may also figure prominently in neoplastic growth. 2009-03-15 2009-04 /pmc/articles/PMC2676236/ /pubmed/19287388 http://dx.doi.org/10.1038/nn.2287 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Chan, Jennifer A.
Balasubramanian, Srividya
Witt, Rochelle M.
Nazemi, Kellie J.
Choi, Yoojin
Pazyra-Murphy, Maria F.
Walsh, Carolyn O.
Thompson, Margaret
Segal, Rosalind A.
Proteoglycan interactions with Sonic Hedgehog specify mitogenic responses
title Proteoglycan interactions with Sonic Hedgehog specify mitogenic responses
title_full Proteoglycan interactions with Sonic Hedgehog specify mitogenic responses
title_fullStr Proteoglycan interactions with Sonic Hedgehog specify mitogenic responses
title_full_unstemmed Proteoglycan interactions with Sonic Hedgehog specify mitogenic responses
title_short Proteoglycan interactions with Sonic Hedgehog specify mitogenic responses
title_sort proteoglycan interactions with sonic hedgehog specify mitogenic responses
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2676236/
https://www.ncbi.nlm.nih.gov/pubmed/19287388
http://dx.doi.org/10.1038/nn.2287
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