Underlying data for quantifications presented.
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Morphogenetic information arises from a combination of genetically encoded cellular properties and emergent cellular behaviors. The spatio-temporal implementation of this information is critical to ensure robust, reproducible tissue shapes, yet the principles underlying its organization remain unknown. We investigated this principle using the mouse auditory epithelium, the organ of Corti (OC). OC consists of a sensory domain, which transduces sound through polar mechanosensory hair cells (HC), part of a mosaic with supporting cells (SC). On either side of the sensory domain are non-sensory domains. These domains undergo cellular rearrangements, which, together, lead to a spiral cochlea that contains planar polarized HCs. This makes the mammalian cochlea a compelling system to understand coordination across spatial scales. Using genetic and ex vivo approaches, we found patterning of OC into sensory and non-sensory domains is associated with a combinatorial expression of adhesion molecules, which underpins OC into spatially defined compartments, enabling planar cell polarity (PCP) cues to regulate compartment-specific organization. Through compartment-specific knockouts of the PCP protein, Vangl2, we find evidence of compartment coupling, a non-linear influence on the organization within one compartment when cellular organization is disrupted in another. In the OC, compartment coupling originates from vinculin-dependent junctional mechanics, coordinating cellular dynamics across spatial scales.
形态发生信息源自遗传编码的细胞特性与涌现性细胞行为的共同作用。该信息的时空执行对于维持稳定且可重复的组织形态至关重要,但其组织构建背后的核心调控原理仍未明确。本研究以小鼠听觉上皮——柯蒂氏器(organ of Corti, OC)——为模型,对该原理展开探究。柯蒂氏器包含感觉结构域,该结构域通过极性机械感觉毛细胞(hair cell, HC)传导声音信号,毛细胞与支持细胞(supporting cell, SC)共同构成镶嵌式结构;感觉结构域的两侧为非感觉结构域。上述两类结构域均会发生细胞重排,二者协同作用最终形成含有平面极性毛细胞的螺旋状耳蜗,这使得哺乳动物耳蜗成为探究跨空间尺度协调机制的理想模型系统。本研究借助遗传学与离体(ex vivo)实验方法,发现柯蒂氏器分化为感觉与非感觉结构域的过程与黏附分子的组合式表达密切相关——该过程为柯蒂氏器构建空间界定的亚区提供了基础,使得平面细胞极性(planar cell polarity, PCP)信号能够调控各亚区的组织构建。通过对平面细胞极性蛋白Vangl2进行亚区特异性基因敲除,我们发现了亚区耦合现象:当某一亚区的细胞组织受到破坏时,会对另一亚区的组织构建产生非线性影响。在柯蒂氏器中,亚区耦合源于纽蛋白(vinculin)依赖的细胞连接力学机制,可协调跨空间尺度的细胞动态变化。



