Ahead of the curve: imaging and computational analysis of shape and form in the developing zebrafish ear

I am originally from Lisbon, Portugal where I completed my undergraduate degree in Evolutionary and Developmental Biology in 2014. I then moved to London, UK to do a MSc in Developmental Neurobiology at Kings College London, which I finished in 2015. Following on, I worked as a research laboratory technician in Lalita Ramakrishnan’s lab at the University of Cambridge for two years. My main research interest is developmental biology, in particular cellular behaviour and cell shape during morphogenesis.

The main aim of my project is to understand how the complex shape of the vertebrate inner ear is generated in the embryo, using the zebrafish as a model. The inner ear is a fluid-filled labyrinth that includes sensitive sensory structures responsible for detecting sound, motion and gravity. In order for the inner ear to function properly, its structures are required to form in the correct position, with the right shape and at the right time during embryonic development. Abnormalities during the inner ear development can lead to deafness and balance disorders. Therefore studying the events that lead to the correct formation of the 3D structure of the inner ear is very important.

Throughout the embryonic development of the inner ear we see several events of tissue folding that seem to be crucial to give the right shape and function to different structures of this organ, in particular those that reveal high levels of curvature. Between 1 and 2 days post fertilization we see the genesis of both the endolymphatic sac and the epithelial projections that initiate formation of the semicircular canals. These are particularly interesting examples of structures generated by epithelial folding in the inner ear, since they seem to be generated in ‘opposite’ ways: the endolymphatic sac shows higher apical curvature, whilst the projections show a higher basal curvature of the epithelium. For this reason, in my project I will be primarily looking at these structures with the following aims:
1. Describe cell shape changes during epithelium folding events seen in early development of the semicircular canals and the endolymphatic sac of the zebrafish inner ear.
2. Identify specific cell behaviours (like cytoskeleton and extracellular matrix arrangements, cellular adhesion changes, etc) and link these to the morphological changes leading to curvature.
3. Apply computational image analysis tools to gain a quantitative appreciation of the morphogenetic changes being studied.

With my research, I hope to provide some insight into how curvature is being driven in the development of the inner ear, contributing to a more detailed knowledge of epithelial folding mechanisms in zebrafish inner ear organogenesis. Moreover, I hope being able to provide a better understanding of the inner ear malformations involved in vestibular disorders.