First Author | Markman S | Year | 2023 |
Journal | Dev Cell | Volume | 58 |
Issue | 7 | Pages | 565-581.e4 |
PubMed ID | 36931270 | Mgi Jnum | J:334725 |
Mgi Id | MGI:7463867 | Doi | 10.1016/j.devcel.2023.02.013 |
Citation | Markman S, et al. (2023) A single-cell census of mouse limb development identifies complex spatiotemporal dynamics of skeleton formation. Dev Cell 58(7):565-581.e4 |
abstractText | 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, non-consecutive, three-dimensional pattern. Single-cell RNA sequencing of the developing mouse forelimb identified 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 an alternative model for limb skeleton development. |