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Structural Basis of Teeth Formation

Nematodes with their cylindrical and uniform body are extremely abundant and are found in all ecosystems. This evolutionary success is largely due to striking adaptations in the head and mouth region (stoma), resulting in a diversity of feeding structures and strategies. For example, the formation of teeth-like denticles in independent nematode lineages is associated with predation and parasitism. Pristionchus pacificus forms two alternative mouth forms, an example of developmental (phenotypic) plasticity. Specifically, the stenostomatous (St) morph with a single tooth and a narrow stoma is a strict bacterial feeder, whereas the eurystomatous (Eu) form with two teeth and a wider stoma is a potential predator of other nematodes and fungi. P. pacificus mouth-form dimorphism has become a major model system to investigate the molecular mechanisms regulating developmental plasticity. However, the structural basis of Pristionchus teeth remained elusive until recently.  

            From ultrastructural analysis it has been suggested that, except for the anterior most part (called cheilostom), the nematode mouth is fully separated from the cuticular exoskeleton. We recently identified the Mucin-type hydrogel-forming protein DPY-6 as a conserved protein component of the mouth with a concomitant role in cuticle formation in P. pacificus and C. elegans (Sun et al. 2022). In humans, Mucin-type proteins are glycoproteins that form a barrier of the mucus. In both P. pacificus and C. elegans, dpy-6 mutant animals have a strongly reduced cheilostom, confirming original hypotheses based on ultrastructural analysis. At the same time, P. pacificus teeth are formed normally in Ppa-dpy-6 mutants indicating that other proteins or macromolecules must form the basis of the teeth in the mouth. Subsequently, we found a major role of chitin in the formation of the teeth-like denticles in P. pacificus (Sun et al., 2023).

Our current work, further explores the role of the DPY-6 protein. We are using two complementary engineering approaches, relying on CRISPR manipulation and biochemical approaches in a collaboration with the Department for Protein Evolution at our Institute.

Scientists involved:

Linxuan Li

Former Scientists: Dr. Shuai Sun

Collaboration: Prof. Andrei Lupas

Selected References:

Sun, S., Witte, H. & Sommer, R. J. (2022): Chitin contributes to the formation of a feeding structure ina predatory nematode. Current Biology, 33, 1-13.

Sun, S., Theska, T., Witte, H., Roedelsperger, C., Ragsdale, E. J. & R. J. Sommer (2021): The Mucin-type hydrogel forming protein DPY-6 has aconserved role in nematode mouth and cuticle formation. Genetics, 220, iyab233.