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RAB23 regulates musculoskeletal development and patterning
RAB23 is a small GTPase which functions at the plasma membrane to regulate growth factor signaling. Mutations in RAB23 cause Carpenter syndrome, a condition that affects normal organogenesis and patterning. In this study, we investigate the role of RAB23 in musculoskeletal development and show that...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9995984/ https://www.ncbi.nlm.nih.gov/pubmed/36910145 http://dx.doi.org/10.3389/fcell.2023.1049131 |
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author | Hasan, Md. Rakibul Koskenranta, Anna Alakurtti, Kirsi Takatalo, Maarit Rice, David P. |
author_facet | Hasan, Md. Rakibul Koskenranta, Anna Alakurtti, Kirsi Takatalo, Maarit Rice, David P. |
author_sort | Hasan, Md. Rakibul |
collection | PubMed |
description | RAB23 is a small GTPase which functions at the plasma membrane to regulate growth factor signaling. Mutations in RAB23 cause Carpenter syndrome, a condition that affects normal organogenesis and patterning. In this study, we investigate the role of RAB23 in musculoskeletal development and show that it is required for patella bone formation and for the maintenance of tendon progenitors. The patella is the largest sesamoid bone in mammals and plays a critical role during movement by providing structural and mechanical support to the knee. Rab23 ( −/− ) mice fail to form a patella and normal knee joint. The patella is formed from Sox9 and scleraxis (Scx) double-positive chondroprogenitor cells. We show that RAB23 is required for the specification of SOX9 and scleraxis double-positive patella chondroprogenitors during the formation of patella anlagen and the subsequent establishment of patellofemoral joint. We find that scleraxis and SOX9 expression are disrupted in Rab23 ( −/− ) mice, and as a result, development of the quadriceps tendons, cruciate ligaments, patella tendons, and entheses is either abnormal or lost. TGFβ-BMP signaling is known to regulate patella initiation and patella progenitor differentiation and growth. We find that the expression of TGFβR2, BMPR1, BMP4, and pSmad are barely detectable in the future patella site and in the rudimentary tendons and ligaments around the patellofemoral joint in Rab23 ( −/− ) mice. Also, we show that GLI1, SOX9, and scleraxis, which regulate entheses establishment and maturation, are weakly expressed in Rab23 ( −/− ) mice. Further analysis of the skeletal phenotype of Rab23 ( −/− ) mice showed a close resemblance to that of Tgfβ2 ( −/− ) mice, highlighting a possible role for RAB23 in regulating TGFβ superfamily signaling. |
format | Online Article Text |
id | pubmed-9995984 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-99959842023-03-10 RAB23 regulates musculoskeletal development and patterning Hasan, Md. Rakibul Koskenranta, Anna Alakurtti, Kirsi Takatalo, Maarit Rice, David P. Front Cell Dev Biol Cell and Developmental Biology RAB23 is a small GTPase which functions at the plasma membrane to regulate growth factor signaling. Mutations in RAB23 cause Carpenter syndrome, a condition that affects normal organogenesis and patterning. In this study, we investigate the role of RAB23 in musculoskeletal development and show that it is required for patella bone formation and for the maintenance of tendon progenitors. The patella is the largest sesamoid bone in mammals and plays a critical role during movement by providing structural and mechanical support to the knee. Rab23 ( −/− ) mice fail to form a patella and normal knee joint. The patella is formed from Sox9 and scleraxis (Scx) double-positive chondroprogenitor cells. We show that RAB23 is required for the specification of SOX9 and scleraxis double-positive patella chondroprogenitors during the formation of patella anlagen and the subsequent establishment of patellofemoral joint. We find that scleraxis and SOX9 expression are disrupted in Rab23 ( −/− ) mice, and as a result, development of the quadriceps tendons, cruciate ligaments, patella tendons, and entheses is either abnormal or lost. TGFβ-BMP signaling is known to regulate patella initiation and patella progenitor differentiation and growth. We find that the expression of TGFβR2, BMPR1, BMP4, and pSmad are barely detectable in the future patella site and in the rudimentary tendons and ligaments around the patellofemoral joint in Rab23 ( −/− ) mice. Also, we show that GLI1, SOX9, and scleraxis, which regulate entheses establishment and maturation, are weakly expressed in Rab23 ( −/− ) mice. Further analysis of the skeletal phenotype of Rab23 ( −/− ) mice showed a close resemblance to that of Tgfβ2 ( −/− ) mice, highlighting a possible role for RAB23 in regulating TGFβ superfamily signaling. Frontiers Media S.A. 2023-02-23 /pmc/articles/PMC9995984/ /pubmed/36910145 http://dx.doi.org/10.3389/fcell.2023.1049131 Text en Copyright © 2023 Hasan, Koskenranta, Alakurtti, Takatalo and Rice. https://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 | Cell and Developmental Biology Hasan, Md. Rakibul Koskenranta, Anna Alakurtti, Kirsi Takatalo, Maarit Rice, David P. RAB23 regulates musculoskeletal development and patterning |
title | RAB23 regulates musculoskeletal development and patterning |
title_full | RAB23 regulates musculoskeletal development and patterning |
title_fullStr | RAB23 regulates musculoskeletal development and patterning |
title_full_unstemmed | RAB23 regulates musculoskeletal development and patterning |
title_short | RAB23 regulates musculoskeletal development and patterning |
title_sort | rab23 regulates musculoskeletal development and patterning |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9995984/ https://www.ncbi.nlm.nih.gov/pubmed/36910145 http://dx.doi.org/10.3389/fcell.2023.1049131 |
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