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Direct BMP signaling to chordoblasts is required for the initiation of segmented notochord sheath mineralization in zebrafish vertebral column development

The vertebral column, with the centra as its iteratively arranged building blocks, represents the anatomical key feature of the vertebrate phylum. In contrast to amniotes, where vertebrae are formed from chondrocytes and osteoblasts deriving from the segmentally organized neural crest or paraxial sc...

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Autores principales: Pogoda, Hans-Martin, Riedl-Quinkertz, Iris, Hammerschmidt, Matthias
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10200950/
https://www.ncbi.nlm.nih.gov/pubmed/37223044
http://dx.doi.org/10.3389/fendo.2023.1107339
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author Pogoda, Hans-Martin
Riedl-Quinkertz, Iris
Hammerschmidt, Matthias
author_facet Pogoda, Hans-Martin
Riedl-Quinkertz, Iris
Hammerschmidt, Matthias
author_sort Pogoda, Hans-Martin
collection PubMed
description The vertebral column, with the centra as its iteratively arranged building blocks, represents the anatomical key feature of the vertebrate phylum. In contrast to amniotes, where vertebrae are formed from chondrocytes and osteoblasts deriving from the segmentally organized neural crest or paraxial sclerotome, teleost vertebral column development is initiated by chordoblasts of the primarily unsegmented axial notochord, while sclerotomal cells only contribute to later steps of vertebrae formation. Yet, for both mammalian and teleostean model systems, unrestricted signaling by Bone Morphogenetic Proteins (BMPs) or retinoic acid (RA) has been reported to cause fusions of vertebral elements, while the interplay of the two signaling processes and their exact cellular targets remain largely unknown. Here, we address this interplay in zebrafish, identifying BMPs as potent and indispensable factors that, as formerly shown for RA, directly signal to notochord epithelial cells/chordoblasts to promote entpd5a expression and thereby metameric notochord sheath mineralization. In contrast to RA, however, which promotes sheath mineralization at the expense of further collagen secretion and sheath formation, BMP defines an earlier transitory stage of chordoblasts, characterized by sustained matrix production/col2a1 expression and concomitant matrix mineralization/entpd5a expression. BMP-RA epistasis analyses further indicate that RA can only affect chordoblasts and their further progression to merely mineralizing cells after they have received BMP signals to enter the transitory col2a1/entpd5a double-positive stage. This way, both signals ensure consecutively for proper mineralization of the notochord sheath within segmented sections along its anteroposterior axis. Our work sheds further light onto the molecular mechanisms that orchestrate early steps of vertebral column segmentation in teleosts. Similarities and differences to BMP’s working mechanisms during mammalian vertebral column formation and the pathomechanisms underlying human bone diseases such as Fibrodysplasia Ossificans Progressiva (FOP) caused by constitutively active BMP signaling are discussed.
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spelling pubmed-102009502023-05-23 Direct BMP signaling to chordoblasts is required for the initiation of segmented notochord sheath mineralization in zebrafish vertebral column development Pogoda, Hans-Martin Riedl-Quinkertz, Iris Hammerschmidt, Matthias Front Endocrinol (Lausanne) Endocrinology The vertebral column, with the centra as its iteratively arranged building blocks, represents the anatomical key feature of the vertebrate phylum. In contrast to amniotes, where vertebrae are formed from chondrocytes and osteoblasts deriving from the segmentally organized neural crest or paraxial sclerotome, teleost vertebral column development is initiated by chordoblasts of the primarily unsegmented axial notochord, while sclerotomal cells only contribute to later steps of vertebrae formation. Yet, for both mammalian and teleostean model systems, unrestricted signaling by Bone Morphogenetic Proteins (BMPs) or retinoic acid (RA) has been reported to cause fusions of vertebral elements, while the interplay of the two signaling processes and their exact cellular targets remain largely unknown. Here, we address this interplay in zebrafish, identifying BMPs as potent and indispensable factors that, as formerly shown for RA, directly signal to notochord epithelial cells/chordoblasts to promote entpd5a expression and thereby metameric notochord sheath mineralization. In contrast to RA, however, which promotes sheath mineralization at the expense of further collagen secretion and sheath formation, BMP defines an earlier transitory stage of chordoblasts, characterized by sustained matrix production/col2a1 expression and concomitant matrix mineralization/entpd5a expression. BMP-RA epistasis analyses further indicate that RA can only affect chordoblasts and their further progression to merely mineralizing cells after they have received BMP signals to enter the transitory col2a1/entpd5a double-positive stage. This way, both signals ensure consecutively for proper mineralization of the notochord sheath within segmented sections along its anteroposterior axis. Our work sheds further light onto the molecular mechanisms that orchestrate early steps of vertebral column segmentation in teleosts. Similarities and differences to BMP’s working mechanisms during mammalian vertebral column formation and the pathomechanisms underlying human bone diseases such as Fibrodysplasia Ossificans Progressiva (FOP) caused by constitutively active BMP signaling are discussed. Frontiers Media S.A. 2023-05-08 /pmc/articles/PMC10200950/ /pubmed/37223044 http://dx.doi.org/10.3389/fendo.2023.1107339 Text en Copyright © 2023 Pogoda, Riedl-Quinkertz and Hammerschmidt 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 Endocrinology
Pogoda, Hans-Martin
Riedl-Quinkertz, Iris
Hammerschmidt, Matthias
Direct BMP signaling to chordoblasts is required for the initiation of segmented notochord sheath mineralization in zebrafish vertebral column development
title Direct BMP signaling to chordoblasts is required for the initiation of segmented notochord sheath mineralization in zebrafish vertebral column development
title_full Direct BMP signaling to chordoblasts is required for the initiation of segmented notochord sheath mineralization in zebrafish vertebral column development
title_fullStr Direct BMP signaling to chordoblasts is required for the initiation of segmented notochord sheath mineralization in zebrafish vertebral column development
title_full_unstemmed Direct BMP signaling to chordoblasts is required for the initiation of segmented notochord sheath mineralization in zebrafish vertebral column development
title_short Direct BMP signaling to chordoblasts is required for the initiation of segmented notochord sheath mineralization in zebrafish vertebral column development
title_sort direct bmp signaling to chordoblasts is required for the initiation of segmented notochord sheath mineralization in zebrafish vertebral column development
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10200950/
https://www.ncbi.nlm.nih.gov/pubmed/37223044
http://dx.doi.org/10.3389/fendo.2023.1107339
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