Understanding the mechanics of tissue development has taken a significant leap forward thanks to new research exploring how forces exerted on developing tissues influence cellular organization. A collaborative study focusing on the Drosophila wing has unveiled how mechanical cues—especially tissue shear—are instrumental in establishing and aligning planar polarity, which is pivotal for proper tissue function and development.
Planar polarity, the uniform orientation of cells along the surface of epithelial tissues, is integral for the correct formation of structures like hair and cilia. The Drosophila wing serves as a model organism for studying this phenomenon due to its well-defined morphological features and the ease of experimental manipulation. The recent findings highlight the role of mechanical forces during tissue morphogenesis as significant contributors to this process.
The researchers confirmed their hypothesis using live imaging techniques to monitor the dynamics of the core planar polarity protein, Frizzled (Fz), across the pupal wing. They found strong correlations between the levels of anisotropic tissue stress—which occurs when tissue is mechanically stretched unevenly—and the behaviors of Fz at intercellular junctions. Specifically, high levels of tissue stress led to decreased stability and accumulation of Fz at cell junctions aligned with the direction of mechanical flow.
High tissue stress anisotropy can reduce the rate of accumulation and lower the stability of core planar polarity proteins. This suggests mechanical cues are not just passive processes but influential actors shaping cellular behavior and orientation.
Observations revealed gradients of cell flow resulting from the contraction of tissue during development, characterized by different velocities across rows of cells. These gradients were found to facilitate the turnover of core protein complexes at junctions, with shear forces exerted during cell displacement being responsible for destabilizing the connections between cells. This creates conditions favorable for planar polarity alignment, which is necessary for subsequent structures to form reliably.
To examine their theory, the team manipulated tissue shear directly by inducing controlled mechanical stress on certain regions of the wing. Under conditions of reduced anisotropic stress, Fz was found to accumulate more rapidly on junctions, highlighting the direct relationship between mechanical forces and cellular responses.
“We propose gradients of cell flow play a role establishing planar polarity,” noted the authors of the article. By establishing and maintaining these cell flow gradients, tissues can reinforce their orientation, effectively guiding the overall polarity of the epithelium.
The methodology utilized included time-lapse imaging and laser ablation techniques, allowing detailed insights even at cellular levels. Measurements taken during 24 to 32 hours after pupal formation indicated refined insights on the correlation between mechanical forces and polarity alignment. Observations during these stages revealed coordinated dynamics of both Fz and actomyosin, thereby providing evidence of the effects of shear forces.
Given the fundamental nature of planar polarity and its evolutionary conservation, the findings have broader consequences for developmental biology. Disruptions to these mechanical processes can lead to severe developmental defects and pathologies, such as birth defects associated with planar polarity defects seen across various organisms, including humans.
Overall, this groundbreaking study sheds light on the complex network of forces at play during tissue development and how they affect core cellular functions. Understanding the nuances of how tissue mechanics influences cellular behavior opens new avenues for research, potentially translating these biological principles to broader biological challenges.
The findings reinforce the notion of mechanical signaling as not merely adjunct to biological processes but as one of the cornerstones upon which proper developmental and morphogenetic processes stand.