Zebrafish Tric-b is required for skeletal development and bone cells differentiation Article Swipe
Francesca Tonelli
,
Laura Leoni
,
Valentina Daponte
,
Roberta Gioia
,
Silvia Cotti
,
Imke A.K. Fiedler
,
Daria Larianova
,
Andy Willaert
,
Paul Coucke
,
Simona Villani
,
Björn Busse
,
Roberta Besio
,
Antonio Rossi
,
P. Eckhard Witten
,
Antonella Forlino
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.3389/fendo.2023.1002914
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.3389/fendo.2023.1002914
Introduction Trimeric intracellular potassium channels TRIC-A and -B are endoplasmic reticulum (ER) integral membrane proteins, involved in the regulation of calcium release mediated by ryanodine (RyRs) and inositol 1,4,5-trisphosphate (IP 3 Rs) receptors, respectively. While TRIC-A is mainly expressed in excitable cells, TRIC-B is ubiquitously distributed at moderate level. TRIC-B deficiency causes a dysregulation of calcium flux from the ER, which impacts on multiple collagen specific chaperones and modifying enzymatic activity, leading to a rare form of osteogenesis imperfecta (OI Type XIV). The relevance of TRIC-B on cell homeostasis and the molecular mechanism behind the disease are still unknown. Results In this study, we exploited zebrafish to elucidate the role of TRIC-B in skeletal tissue. We demonstrated, for the first time, that tmem38a and tmem38b genes encoding Tric-a and -b, respectively are expressed at early developmental stages in zebrafish, but only the latter has a maternal expression. Two zebrafish mutants for tmem38b were generated by CRISPR/Cas9, one carrying an out of frame mutation introducing a premature stop codon ( tmem38b -/- ) and one with an in frame deletion that removes the highly conserved KEV domain ( tmem38b Δ120-7/Δ120-7 ). In both models collagen type I is under-modified and partially intracellularly retained in the endoplasmic reticulum, as described in individuals affected by OI type XIV. Tmem38b -/- showed a mild skeletal phenotype at the late larval and juvenile stages of development whereas tmem38b Δ120-7/Δ120-7 bone outcome was limited to a reduced vertebral length at 21 dpf. A caudal fin regeneration study pointed towards impaired activity of osteoblasts and osteoclasts associated with mineralization impairment. Discussion Our data support the requirement of Tric-b during early development and for bone cell differentiation.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.3389/fendo.2023.1002914
- https://www.frontiersin.org/articles/10.3389/fendo.2023.1002914/pdf
- OA Status
- gold
- Cited By
- 14
- References
- 67
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4317717864
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4317717864Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.3389/fendo.2023.1002914Digital Object Identifier
- Title
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Zebrafish Tric-b is required for skeletal development and bone cells differentiationWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2023Year of publication
- Publication date
-
2023-01-23Full publication date if available
- Authors
-
Francesca Tonelli, Laura Leoni, Valentina Daponte, Roberta Gioia, Silvia Cotti, Imke A.K. Fiedler, Daria Larianova, Andy Willaert, Paul Coucke, Simona Villani, Björn Busse, Roberta Besio, Antonio Rossi, P. Eckhard Witten, Antonella ForlinoList of authors in order
- Landing page
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https://doi.org/10.3389/fendo.2023.1002914Publisher landing page
- PDF URL
-
https://www.frontiersin.org/articles/10.3389/fendo.2023.1002914/pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
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https://www.frontiersin.org/articles/10.3389/fendo.2023.1002914/pdfDirect OA link when available
- Concepts
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Zebrafish, Cell biology, Biology, Bone development, Anatomy, Genetics, Endocrinology, GeneTop concepts (fields/topics) attached by OpenAlex
- Cited by
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14Total citation count in OpenAlex
- Citations by year (recent)
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2025: 8, 2024: 4, 2023: 2Per-year citation counts (last 5 years)
- References (count)
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67Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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| corresponding_author_ids | https://openalex.org/A5033142948 |
| countries_distinct_count | 3 |
| institutions_distinct_count | 15 |
| corresponding_institution_ids | https://openalex.org/I25217355 |
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| sustainable_development_goals[0].display_name | Life below water |
| citation_normalized_percentile.value | 0.95393626 |
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| citation_normalized_percentile.is_in_top_10_percent | True |