Chordacentrum mineralization is delayed in zebrafish betaglycan‐null mutants

• Published in: Developmental dynamics 2022-01, Vol.251 (1), p.213-225
• Main Authors: Molina‐Villa, Tonatiuh, Ramírez‐Vidal, Lizbeth, Mendoza, Valentín, Escalante‐Alcalde, Diana, López‐Casillas, Fernando
• Format: Article
• Language: English
• Subjects: Abnormalities; Angiogenesis; Animals; betaglycan; chordacentra; CRISPR; Danio rerio; Embryos; Growth factors; Kidneys; Ligands; Mice; Mineralization; Mutants; Phenotypes; Proteoglycans - genetics; Receptors; Receptors, Transforming Growth Factor beta - genetics; Receptors, Transforming Growth Factor beta - metabolism; Signal processing; Signal transduction; Signal Transduction - genetics; Signaling; TGFBR3; TGF‐beta; Transforming Growth Factor beta - genetics; Transforming Growth Factor beta - metabolism; Transforming growth factor-b; Vertebrae; Zebrafish; Zebrafish - genetics; Zebrafish - metabolism
• ISSN: 1058-8388; 1097-0177
• DOI: 10.1002/dvdy.393

Background The Transforming Growth Factor β (TGFβ) family is a group of related proteins that signal through a type I and type II receptors. Betaglycan, also known as the type III receptor (Tgfbr3), is a coreceptor for various ligands of the TGFβ family that participates in heart, liver and kidney development as revealed by the tgfbr3‐null mouse, as well as in angiogenesis as revealed by Tgfbr3 downregulation in morphant zebrafish. Results Here, we present CRISPR/Cas9‐derived zebrafish Tgfbr3‐null mutants, which exhibited unaltered embryonic angiogenesis and developed into fertile adults. One reproducible phenotype displayed by these Tgfbr3‐null mutants is delayed chordacentra mineralization, which nonetheless does not result in vertebral abnormalities in the adult fishes. We also report that the canonical TGFβ signaling pathway is needed for proper chordacentra mineralization and that Tgfbr3 absence decreases this signal in the notochordal cells responsible for this process. Conclusion Betaglycan's “ligand presentation” function contributes to the optimal TGFβ signaling required for zebrafish chordacentra mineralization. Key Findings Zebrafish betaglycan gene null mutants are viable and fertile without major obvious defects. Delayed chordocentra mineralization is a reproducible phenotype in these animals. This phenotype can be accounted for by a deficient TGF‐beta signaling in chordocentra, very likely due to the lack of betaglycan TGF‐beta presentation function. This is the first time this function is documented in vivo.