For the work carried out in this fellowship, we have studied the dynamics of this process, called planar cell inversion in high detail using live microscopy tracking and computational modelling.
Imagine a dance floor in which a couple, a man and a woman, enter and position themselves in the center of the room. They face each other. New couples enter regularly and they go to dance next to the first couple, after a while, you have all the men looking in the same direction: where the women are, and reciprocally, all women are facing in the same direction, toward the men. Any new couple entering the room can see if they have entered in the "correct" position, if not, they will rotate 180 deg until they join the group and the man is facing towards his partner and all the other women, and vice versa.
Believe it or not, something very similar happens when new hair cells originate in a neuromast. The 180 degree swirl that cells perform is what we called planar cell inversion.
Using a fluorescent microscope, we filmed the process at a resolution that allowed us to measure the velocity, angle, and shape of many cells as they rotate, to characterize the statistics of the process. We then compared the normal rotations to two genetic perturbations known to alter the identity of the hair cells in opposite ways. In the dance floor analogy, this would be like to putting a tuxedo to all participants, or conversely, a dress. To our surprise, these perturbations do very little to alter the dynamics of planar cell inversion. The results of this investigation will be published in a future manuscript.
A mutation in a different gene, called Wnt, affects the orientation of hair cells in a different way. Instead of hair cells being oriented in one direction, or the other, the whole collective forms a swirl, or a spiral pattern. We realized that the formation of the spiral pattern could be explained solely in terms of physical interactions between the cells. The physics involved have been used to describe completely different phenomena in liquid crystals, magnetic systems, and crowds in a hard rock concert. Therefore, the analogy with the dance room is not so misplaced. The physics models describe the formation of complex patterns solely by the interaction of agents with an orientation, where the "agent" can be a hair cell, a spins in a magnet, or a person in a crowd. The results of this study will also be eventually published in a paper on the mechanisms of neuromast patterning.
Along the future papers, and according to the data management plan, we will freely share the data from microscopy images for three reasons: (i) to make our work easier to understand and reproduce. (ii) because microscopy images contain multidimensional data that other researchers/students might use to generate new hypotheses. (iii) the annotated data might be useful to refine machine learning models that extract quantitative features from images of cells.
