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bioRxiv · 10.1101/2022.05.07.490557

Single-cell atlas of mouse limb development reveals a complex spatiotemporal dynamics of skeleton formation

Markman, S.·Zada, M.·David, E.·Giladi, A.·Amit, I.·Zelzer, E.
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Abstract

Limb development has long served as a model system for coordinated spatial patterning of progenitor cells. Here, we identify a population of naive limb progenitors and show that they differentiate progressively to form the skeleton in a complex nonconsecutive three-dimensional pattern. Single-cell RNA sequencing of the developing mouse forelimb revealed three progenitor states: naive, proximal and autopodial, as well as Msx1 as a marker for the naive progenitors. In vivo lineage tracing confirmed this role and localized the naive progenitors to the outer margin of the limb, along the anterior-posterior axis. Sequential pulse-chase experiments showed that the progressive transition of Msx1+ naive progenitors into proximal and autopodial progenitors coincides with their differentiation to Sox9+ chondroprogenitors, which occurs along all the forming skeletal segments. Indeed, tracking the spatiotemporal sequence of differentiation showed that the skeleton forms progressively in a complex pattern. These findings suggest a new model for limb skeleton development.

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Markman, S., Zada, M., David, E., Giladi, A., Amit, I., Zelzer, E.. 2022-05-07. Single-cell atlas of mouse limb development reveals a complex spatiotemporal dynamics of skeleton formation. https://doi.org/10.1101/2022.05.07.490557

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