Abstract

In our group we wonder how developing organs “know” how much they must grow in order to attain and maintain species-specific body proportions, and how this collective outcome emerges from the combination of individual cell behaviours. We use the vertebrate limb as a model, and while long bones in the limbs are our starting point, we also study how they crosstalk with other connective tissues and with distant organs. In this talk, I will provide a taste of three main projects:

Cellular and molecular mechanisms of catch-up growth One powerful approach to study the regulation of organ size is analysing how organs recover a normal growth trajectory after a developmental insult, which is known as catch-up growth. Using lineage tracing and genomics approaches, we are unveiling new mechanisms that trigger the compensatory response upon insult.

Identifying the sizostat (a thermostat for size) Classic experiments suggested that there is a target bone-size-for-age, and that a feedback mechanism informs cartilage cells of bone size. We think that this mechanism works as a thermostat, and we are exploring the underlying biophysical and molecular mechanisms.

Using inter-species chimeras to identify the determinants of limb size A classic approach to distinguish between intrinsic and extrinsic determinants of organ development is to cause the organ to develop in the body of a different species. We are striving to generate chimeric animals in which rat or jerboa stem cells will give rise to the limb tissues in the context of a mouse embryo, in order to study the gene regulatory regions involved in size adaptation.

I will discuss how these projects not only address fundamental knowledge gaps, but may also provide new avenues for growth therapies and regenerative medicine.