Muñoz-Montecinos Carlos, Romero Adrián, Sepúlveda Vania, Vira María Ángela, Fehrmann-Cartes Karen, Marcellini Sylvain, Aguilera Felipe, Caprile Teresa, Fuentes Ricardo
Departamento de Biología Celular, Facultad de Ciencias Biológicas, Universidad de Concepción, Concepción, Chile.
Grupo de Procesos en Biología del Desarrollo (GDeP), Facultad de Ciencias Biológicas, Universidad de Concepción, Concepción, Chile.
Front Cell Dev Biol. 2022 Jan 26;9:801652. doi: 10.3389/fcell.2021.801652. eCollection 2021.
The vertebral column, or spine, provides mechanical support and determines body axis posture and motion. The most common malformation altering spine morphology and function is adolescent idiopathic scoliosis (AIS), a three-dimensional spinal deformity that affects approximately 4% of the population worldwide. Due to AIS genetic heterogenicity and the lack of suitable animal models for its study, the etiology of this condition remains unclear, thus limiting treatment options. We here review current advances in zebrafish phenogenetics concerning AIS-like models and highlight the recently discovered biological processes leading to spine malformations. First, we focus on gene functions and phenotypes controlling critical aspects of postembryonic aspects that prime in spine architecture development and straightening. Second, we summarize how primary cilia assembly and biomechanical stimulus transduction, cerebrospinal fluid components and flow driven by motile cilia have been implicated in the pathogenesis of AIS-like phenotypes. Third, we highlight the inflammatory responses associated with scoliosis. We finally discuss recent innovations and methodologies for morphometrically characterize and analyze the zebrafish spine. Ongoing phenotyping projects are expected to identify novel and unprecedented postembryonic gene functions controlling spine morphology and mutant models of AIS. Importantly, imaging and gene editing technologies are allowing deep phenotyping studies in the zebrafish, opening new experimental paradigms in the morphometric and three-dimensional assessment of spinal malformations. In the future, fully elucidating the phenogenetic underpinnings of AIS etiology in zebrafish and humans will undoubtedly lead to innovative pharmacological treatments against spinal deformities.
脊柱，即脊椎，提供机械支撑并决定身体轴线的姿势和运动。改变脊柱形态和功能最常见的畸形是青少年特发性脊柱侧凸（AIS），这是一种三维脊柱畸形，影响全球约4%的人口。由于AIS的遗传异质性以及缺乏适合研究它的动物模型，这种疾病的病因仍不清楚，从而限制了治疗选择。我们在此回顾斑马鱼表型遗传学在类AIS模型方面的当前进展，并强调最近发现的导致脊柱畸形的生物学过程。首先，我们关注控制胚胎后脊柱结构发育和矫正关键方面的基因功能和表型。其次，我们总结了初级纤毛组装和生物力学刺激转导、脑脊液成分以及由运动纤毛驱动的脑脊液流动如何与类AIS表型的发病机制相关。第三，我们强调与脊柱侧凸相关的炎症反应。我们最后讨论了用于形态学表征和分析斑马鱼脊柱的最新创新和方法。正在进行的表型分析项目有望识别控制脊柱形态的新的和前所未有的胚胎后基因功能以及AIS的突变模型。重要的是，成像和基因编辑技术正在使斑马鱼的深度表型分析研究成为可能，为脊柱畸形的形态学和三维评估开辟了新的实验范式。未来，全面阐明斑马鱼和人类中AIS病因的表型遗传学基础无疑将带来针对脊柱畸形的创新药物治疗。
