Development of scales and the hyomandibular bone in zebrafish through ECM remodeling

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K16146
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 44020:Developmental biology-related
• Research Institution: Kitasato University
• Principal Investigator: Iwasaki Miki 北里大学, 一般教育部, 非常勤講師 (70792563)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: ゼブラフィッシュ / 骨組織 / MMP / ECM / パターン形成

Outline of Final Research Achievements

Development of scales and the hyomandibular bone in zebrafish, and revealed that Matrix metalloproteinase 9(mmp9), which degrades the extracellular matrix (ECM), is expressed in groove and ridge of scales, and around the hyomandibular (Hm)foramen. We showed that ablation of mmp9-expressing cells of scales regeneration, resulted in significant reduction of groove, suggesting a role of mmp9 in scale morphogenesis.
In the hyomandibular bone, mmp9:GFP is expressed in Schwann cells myelinating the facial nerve passing thorough the Hm foramen.The genetical ablation of Schwann cells reduced size of the Hm foramen accompanied by excess hypertrophy of chondrocyte. Further, mmp9:GFP-expressing osteoclasts are required for enlargement of the Hm foramen by bone resorption. In the csfr-/- mutant fish, in which osteoclasts activities are impaired, enlargement of the Hm foramen was severely affected. These results show that mmp9 is essential for degradation of ECM during bone morphogenesis.

Free Research Field

発生生物学

Academic Significance and Societal Importance of the Research Achievements

骨の形態形成には、複数の細胞(骨芽細胞・破骨細胞・軟骨細胞)と細胞外基質が協調して働いている。これらの細胞同士がどのように相互作用しているのかよく分かっていない。この研究では、骨芽細胞や破骨細胞による骨リモデリングが骨の形態を制御するだけではなく、軟骨基質、骨基質の分解が重要な役割を担うことを示した。その制御を担う分子としてmmp9を同定した。今後、mmp9の機能解析によって、分解する基質を明らかにし、そのとき生じる周囲の細胞の動態を調べることで、これまで知られていない骨の形態形成メカニズムを解明できると考えている。