Balance Between Tooth Size and Tooth Number Is Controlled by Hyaluronan

While the function of proteins and genes has been widely studied during vertebrate development, relatively little work has addressed the role of carbohydrates. Hyaluronan (HA), also known as hyaluronic acid, is an abundant carbohydrate in embryonic tissues and is the main structural component of the...

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Autores principales: Sánchez, Natalia, González-Ramírez, María Constanza, Contreras, Esteban G., Ubilla, Angélica, Li, Jingjing, Valencia, Anyeli, Wilson, Andrés, Green, Jeremy B. A., Tucker, Abigail S., Gaete, Marcia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7476214/
https://www.ncbi.nlm.nih.gov/pubmed/32982773
http://dx.doi.org/10.3389/fphys.2020.00996
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author Sánchez, Natalia
González-Ramírez, María Constanza
Contreras, Esteban G.
Ubilla, Angélica
Li, Jingjing
Valencia, Anyeli
Wilson, Andrés
Green, Jeremy B. A.
Tucker, Abigail S.
Gaete, Marcia
author_facet Sánchez, Natalia
González-Ramírez, María Constanza
Contreras, Esteban G.
Ubilla, Angélica
Li, Jingjing
Valencia, Anyeli
Wilson, Andrés
Green, Jeremy B. A.
Tucker, Abigail S.
Gaete, Marcia
author_sort Sánchez, Natalia
collection PubMed
description While the function of proteins and genes has been widely studied during vertebrate development, relatively little work has addressed the role of carbohydrates. Hyaluronan (HA), also known as hyaluronic acid, is an abundant carbohydrate in embryonic tissues and is the main structural component of the extracellular matrix of epithelial and mesenchymal cells. HA is able to absorb large quantities of water and can signal by binding to cell-surface receptors. During organ development and regeneration, HA has been shown to regulate cell proliferation, cell shape, and migration. Here, we have investigated the function of HA during molar tooth development in mice, in which, similar to humans, new molars sequentially bud off from a pre-existing molar. Using an ex vivo approach, we found that inhibiting HA synthesis in culture leads to a significant increase in proliferation and subsequent size of the developing molar, while the formation of sequential molars was inhibited. By cell shape analysis, we observed that inhibition of HA synthesis caused an elongation and reorientation of the major cell axes, indicating that disruption to cellular orientation and shape may underlie the observed phenotype. Lineage tracing demonstrated the retention of cells in the developing first molar (M1) at the expense of the generation of a second molar (M2). Our results highlight a novel role for HA in controlling proliferation, cell orientation, and migration in the developing tooth, impacting cellular decisions regarding tooth size and number.
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spelling pubmed-74762142020-09-26 Balance Between Tooth Size and Tooth Number Is Controlled by Hyaluronan Sánchez, Natalia González-Ramírez, María Constanza Contreras, Esteban G. Ubilla, Angélica Li, Jingjing Valencia, Anyeli Wilson, Andrés Green, Jeremy B. A. Tucker, Abigail S. Gaete, Marcia Front Physiol Physiology While the function of proteins and genes has been widely studied during vertebrate development, relatively little work has addressed the role of carbohydrates. Hyaluronan (HA), also known as hyaluronic acid, is an abundant carbohydrate in embryonic tissues and is the main structural component of the extracellular matrix of epithelial and mesenchymal cells. HA is able to absorb large quantities of water and can signal by binding to cell-surface receptors. During organ development and regeneration, HA has been shown to regulate cell proliferation, cell shape, and migration. Here, we have investigated the function of HA during molar tooth development in mice, in which, similar to humans, new molars sequentially bud off from a pre-existing molar. Using an ex vivo approach, we found that inhibiting HA synthesis in culture leads to a significant increase in proliferation and subsequent size of the developing molar, while the formation of sequential molars was inhibited. By cell shape analysis, we observed that inhibition of HA synthesis caused an elongation and reorientation of the major cell axes, indicating that disruption to cellular orientation and shape may underlie the observed phenotype. Lineage tracing demonstrated the retention of cells in the developing first molar (M1) at the expense of the generation of a second molar (M2). Our results highlight a novel role for HA in controlling proliferation, cell orientation, and migration in the developing tooth, impacting cellular decisions regarding tooth size and number. Frontiers Media S.A. 2020-08-24 /pmc/articles/PMC7476214/ /pubmed/32982773 http://dx.doi.org/10.3389/fphys.2020.00996 Text en Copyright © 2020 Sánchez, González-Ramírez, Contreras, Ubilla, Li, Valencia, Wilson, Green, Tucker and Gaete. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Sánchez, Natalia
González-Ramírez, María Constanza
Contreras, Esteban G.
Ubilla, Angélica
Li, Jingjing
Valencia, Anyeli
Wilson, Andrés
Green, Jeremy B. A.
Tucker, Abigail S.
Gaete, Marcia
Balance Between Tooth Size and Tooth Number Is Controlled by Hyaluronan
title Balance Between Tooth Size and Tooth Number Is Controlled by Hyaluronan
title_full Balance Between Tooth Size and Tooth Number Is Controlled by Hyaluronan
title_fullStr Balance Between Tooth Size and Tooth Number Is Controlled by Hyaluronan
title_full_unstemmed Balance Between Tooth Size and Tooth Number Is Controlled by Hyaluronan
title_short Balance Between Tooth Size and Tooth Number Is Controlled by Hyaluronan
title_sort balance between tooth size and tooth number is controlled by hyaluronan
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7476214/
https://www.ncbi.nlm.nih.gov/pubmed/32982773
http://dx.doi.org/10.3389/fphys.2020.00996
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