Research Summary: Using a combination of experiments and mathematical modelling, we show that the tuned differences in the mechanical properties of junctions can organise cells into precise patterns.
Author interview: Anubhav Prakash is an experimentalist interested in understanding how developing organs integrate a multitude of biochemical and mechanical information to generate robust shapes and patterns. He did his Bachelor’s in Botany from Hansraj College, University of Delhi, before obtaining his PhD from NCBS, under the supervision of Prof Raj Ladher.
Lab: Prof Raj Ladher, NCBS, Tata Institute of Fundamental Research
Lab social media: @earlab.bsky.social | Twitter
What was the core problem you aimed to solve with this research?
Proper functioning of every organ depends on the characteristics of the cells and their precise organisation. In auditory epithelia, there are two cell types: one is the mechanosensory hair cells (HCs), which transmit the sound to the brain, and the other is supporting cells (SCs). HCs perform the function of converting sound to a neuronal signal by a specialised structure on their apical surface called a hair bundle. For optimal functioning, these hair bundles of each HCs should point in the same direction, and the HCs are always surrounded by SCs.
In our research, we aimed to investigate the mechanism that drives the organisation of HCs and SC, as well as aligns the asymmetric hair bundle among HCs.
How did you go about solving this problem?
We started with quantifying the developmental trajectories of both these organisations in the avian auditory epithelia, called the Basilar Papilla (BP). We found that both the spatial organisation of HC and SC and the alignment of hair bundles emerge at the same time, and the perturbation of spatial organisation leads to defects in hair bundle alignment. This allowed us to think about a mechanism that could drive both organisations.
We thought about spatial organisation, as it was intuitive, the larger the cell, the more neighbours (Lewis Law). In BP, at equal surface area, HCs and SCs had different neighbours, suggesting they were mechanically different. We found the interface between two SCs showed higher contractility compared to the interface between an HC and SC, governed by the localisation of differentially phosphorylated non-muscle myosin. As we expected, these junctional differences were critical for the development of spatial organisation and somehow also aligned hair bundles.
We then build a mathematical model incorporating these junctional differences and hypothesise how the junctional asymmetries can develop hair bundle alignment. After testing multiple possibilities, we find that the asymmetric localisation of a protein, Vangl2, on the SC-SC interface drives double phosphorylated forms of NMII, which form an asymmetric tissue axis. In HCs, the cues (LGN-Gai) that govern the formation of the asymmetric hair bundle also regulate the asymmetry of myosin phosphorylation at the HC-SC interface.
These two asymmetries drive the concurrent development of spatial organisation and hair bundle alignment.
How would you explain your research outcomes (Key findings) to the non-scientific community?
The functioning of every organ in our body is dependent upon how cells are organised. Like in our eyes, the white part surrounds the black part, like the nails are at the top of the finger. Our results say that this organisation is dependent upon the interface between the cells.
The study is a great example of biology and physics coming together. Anubhav has found that the design rules that govern how cells organise in a tissue are actually pretty simple, and tuned contractility is enough to make patterns.
What are the potential implications of your findings for the field and society?
This work is a stepping stone for us. We are now able to think that the cellular patterns in organs are a combination of spatial organisation and directional alignment. We and others are now interested in asking how a more complex organisation with multiple cell types (rather than two in BP) develops and are investigating to find the additional molecular details that govern the differences in junctional properties.
We are leading to see an impact on society in two ways, one: the molecules that govern the differences in cellular interface are linked to children with defects. We are trying to understand the mechanisms of these molecules so that we can develop therapeutic interventions. Second: this work would allow us to form a miniature functional organ on a petri dish, and we could test new drugs, speeding up the drug discovery.
What was the exciting moment during your research?
For me, science never gives us a dull moment. If I have to pick one, it would be when we could rescue the deformed BP to a correct form. This reversal opened a lot of possibilities, it became the most exciting part of the journey.
Paper reference: Prakash, A., Weninger, J., Singh, N. et al. Junctional force patterning drives both positional order and planar polarity in the auditory epithelia. Nat Commun 16, 3927 (2025). https://doi.org/10.1038/s41467-025-58557-0
