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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Frontiers Media S.A.
2023-05-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2023.1107339/full |
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| author | Hans-Martin Pogoda Iris Riedl-Quinkertz Matthias Hammerschmidt Matthias Hammerschmidt Matthias Hammerschmidt |
| author_facet | Hans-Martin Pogoda Iris Riedl-Quinkertz Matthias Hammerschmidt Matthias Hammerschmidt Matthias Hammerschmidt |
| author_sort | Hans-Martin Pogoda |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-09T13:56:54Z |
| format | Article |
| id | doaj.art-88cf3704eef04f3d949b6271b1354f16 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-04-09T13:56:54Z |
| publishDate | 2023-05-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Endocrinology |
| spelling | doaj.art-88cf3704eef04f3d949b6271b1354f162023-05-08T04:34:58ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-05-011410.3389/fendo.2023.11073391107339Direct BMP signaling to chordoblasts is required for the initiation of segmented notochord sheath mineralization in zebrafish vertebral column developmentHans-Martin Pogoda0Iris Riedl-Quinkertz1Matthias Hammerschmidt2Matthias Hammerschmidt3Matthias Hammerschmidt4Institute of Zoology – Developmental Biology, University of Cologne, Cologne, GermanyInstitute of Zoology – Developmental Biology, University of Cologne, Cologne, GermanyInstitute of Zoology – Developmental Biology, University of Cologne, Cologne, GermanyCluster of Excellence, Cellular Stress Responses in Aging-Associated Diseases (CECAD) Cluster of Excellence, University of Cologne, Cologne, GermanyCenter for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, GermanyThe 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.https://www.frontiersin.org/articles/10.3389/fendo.2023.1107339/fullnotochordchordoblastBMPretinoic acidvertebral bodycentra |
| spellingShingle | Hans-Martin Pogoda Iris Riedl-Quinkertz Matthias Hammerschmidt Matthias Hammerschmidt Matthias Hammerschmidt Direct BMP signaling to chordoblasts is required for the initiation of segmented notochord sheath mineralization in zebrafish vertebral column development Frontiers in Endocrinology notochord chordoblast BMP retinoic acid vertebral body centra |
| 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 | notochord chordoblast BMP retinoic acid vertebral body centra |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2023.1107339/full |
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