分区的机械耦合驱动小鼠听觉上皮细胞的极性和模式化

Anubhav Prakash, Sukanya Raman, Raman Kaushik, Anton S Iyer, Raj K Ladher
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摘要

驱动形态发生的信息不仅取决于基因编码的细胞特性,还来自这些细胞行为之间的相互作用。这种信息在空间和时间上的实施,使组织的形状和秩序在发育过程中具有稳健性和可重复性。组织这些信息的原则是什么?小鼠的听觉上皮--柯蒂耳器(OC)是研究这一问题的绝佳系统。中央区域通过机械感觉毛细胞(HC)感知声音信息,HC 是与支持细胞(SC)镶嵌在一起的一部分。两侧是非感觉域。这些结构域在有序伸长的过程中会发生细胞重排。细胞特性如何在不同结构域之间协调,以及这些特性如何对组织形状做出贡献,目前尚不清楚。在这里,我们发现通过形态发生器模式化建立的粘附代码将 OC 域定义为区室。每个区室中的细胞都表现出不同的排序模式。通过扰乱单个区室中的细胞重排,我们发现特定区室的有序性可以促进整体组织结构的形成。扰乱一个区室的细胞有序也会影响另一个区室的组织。通过使用 vinculin 突变体,我们发现区室间的耦合在一定程度上是机械性的。我们的研究表明,在器官形成过程中,细胞区室及其耦合可以在空间和时间上组织形态发生信息。
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Mechanical coupling of compartments drives polarity and patterning of mouse auditory epithelium
The information that drives morphogenesis depends not only on genetically encoded cellular properties, but also emerges from the interaction between these cell behaviours. This information is spatio-temporally implemented to make tissue shape and order robust and reproducible during development. What are the principles for organising this information? The mouse auditory epithelium, the organ of Corti (OC) is an excellent system to investigate this. A central domain senses sound information through mechanosensory hair cells (HC), part of a mosaic with supporting cells (SC). This is flanked by non-sensory domains. These domains undergo cellular rearrangements as they become ordered and elongate. How cellular properties are coordinated across domains and how these contribute to tissue shape is unknown. Here, we find adhesion codes, established through morphogen patterning, define OC domains as compartments. Cells in each compartment exhibit distinct patterns of ordering. By perturbing cellular rearrangements in individual compartments, we find that compartment-specific ordering can contribute to overall tissue architecture. Perturbation of cell order within a compartment also affects the organisation in another. Using vinculin mutants, we show that inter-compartment coupling is, in part, mechanical. Our work suggests that compartments and their coupling can organise morphogenetic information in space and time during organogenesis.
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