Essential Role of Nr2f Nuclear Receptors in Patterning the Vertebrate Upper Jaw
Essential Role of Nr2f Nuclear Receptors in Patterning the Vertebrate Upper Jaw
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DOI：
10.1016/j.devcel.2017.12.022
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发表时间：
2018-02-05
影响因子：
11.8
通讯作者：
Crump, J. Gage
中科院分区：
文献类型：
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作者：
Barske, Lindsey;Rataud, Pauline;Crump, J. Gage
下颌是脊椎动物各种摄食和捕食行为的核心。下颌骨而非上颌骨是围绕早期发育的软骨模板形成的。虽然内皮素 1 决定了下颌的形态，但决定上颌形态的因素仍然难以捉摸。在这里，我们鉴定出核受体 2f 基因 (Nr2fs) 在斑马鱼上颌形成中富集并为上颌形成所必需。 Nr2fs 的组合损失将上颌的上颌骨组件转变为下颌样结构。相反，nr2f5 错误表达会破坏下颌发育。全基因组分析表明，Nr2fs 抑制下颌基因表达和上颌前体的早期软骨形成。通过减少 Nr2f 剂量来挽救内皮素 1 突变体的下颌缺陷进一步表明，为了正常的下颌发育，必须抑制 Nr2f 的表达。我们认为，Nr2fs 通过保护上颌祖细胞免受早期软骨形成的影响来塑造上颌，从而为以后的成骨保留细胞。
The jaw is central to the extensive variety of feeding and predatory behaviors across vertebrates. The bones of the lower but not upper jaw form around an early-developing cartilage template. Whereas Endothelin1 patterns the lower jaw, the factors that specify upper-jaw morphology remain elusive. Here, we identify Nuclear Receptor 2f genes (Nr2fs) as enriched in and required for upper-jaw formation in zebrafish. Combinatorial loss of Nr2fs transforms maxillary components of the upper jaw into lower-jaw- like structures. Conversely, nr2f5 misexpression disrupts lower-jaw development. Genome-wide analyses reveal that Nr2fs repress mandibular gene expression and early chondrogenesis in maxillary precursors. Rescue of lower-jaw defects in endothelin1 mutants by reducing Nr2f dosage further demonstrates that Nr2f expression must be suppressed for normal lower-jaw development. We propose that Nr2fs shape the upper jaw by protecting maxillary progenitors from early chondrogenesis, thus preserving cells for later osteogenesis.