Probing morphodynamic truth: an exploratory cross-sectional analysis of cytoskeletal modulation symptoms and protrusion behaviour in a juvenile epithelial cohort
June 27
Protrusion behaviour derived from high-frequency time-lapse microscopy metadata is an emerging morphogenetic phenotype that may assist in diagnosing and monitoring developmental dysregulation. While cytoskeletal hyperactivity and quiescence have been hypothesised as morphological symptoms that may influence protrusion behaviour, no studies have directly tested this assumption. Here, we tested whether specific developmental symptoms were associated with various protrusion features in juvenile epithelial sheets. Juvenile samples from an Australasian cohort study (n = 895) completed a standardised wound-healing assay under live imaging. Common features of protrusion timing (i.e., median dwell, extension interval, retraction latency, extension–extension time, and retraction–retraction time) and frequency (i.e., total protrusions, retractions, lamellipodial events, retraction ratio, and lamellipodial ratio) were extracted. Developmental symptoms were assessed using the Morphogenesis Inventory–Juvenile version (MI-J). Multiple linear regression models were used to test associations between symptom items and protrusion features. Non-linear effects and moderating effects of genetic sex were also explored.
Cytoskeletal activity symptoms (i.e., MI-J item 8) were not associated with protrusion timing or frequency. However, elevated nutrient-uptake symptoms (i.e., MI-J item 5) were associated with faster extension–extension time and a greater number of total protrusions. Symptoms of bioelectric quiescence (i.e., MI-J item 1) showed non-linear associations with protrusion features. The results do not support a relationship between cytoskeletal activity symptoms and protrusion behaviour in juvenile epithelia. However, nutrient-related symptoms were associated with faster and more frequent protrusive activity. Further research into the relationship between morphodynamic behaviour and developmental status in young tissues is warranted.