A population intrinsic timer controlsHoxgene expression and cell dispersion during progenitor addition to the body axis

Abstract

During embryonic development, the timing of events at the cellular level must be coordinated across multiple length scales to ensure the formation of a well-proportioned body plan. This is clear during somitogenesis, where the progenitors must be allocated to the axis over time whilst maintaining a progenitor population for continued elaboration of the body plan. However, the relative importance of intrinsic and extrinsic signals in timing progenitor addition at the single cell level is not yet understood. Heterochronic grafts from older to younger embryos have suggested a level of intrinsic timing whereby later staged cells contribute to more posterior portions of the axis. To determine the precise step at which cells are delayed, we performed single-cell transcriptomic analysis on heterochronic grafts of somite progenitors in the chicken embryo. This revealed a previously undescribed cell state within which heterochronic grafted cells are stalled, post-ingression through the primitive streak. The delayed exit of older cells from this state correlates with expression of posterior Hox genes. Using grafting and explant culture, we find that both Hox gene expression and the migratory capabilities of progenitor populations are intrinsically regulated at the population level. Therefore, we demonstrate that cell dispersion is controlled by a population intrinsic timer to control progenitor addition to the presomitic mesoderm.

Species-specific roles of the Notch ligands, receptors, and targets orchestrating the signaling landscape of the segmentation clock

“…Similar results have been reported in small-sized zebrafish embryos, which show a smaller somite size such that the somite number remains unchanged ( Ishimatsu et al, 2018 ). Another recent study has also re-enforced the view of a pre-pattern by performing grafts of the primitive streak (PS) from older (HH8) to younger (HH4) chick embryos ( Busby et al, 2023 ). While GFP + grafts from an HH4 PS to an HH4 PS appeared in more anterior (first formed) somites, grafts from an HH8 PS transplanted into HH4 only populated the posterior (later formed) somites.…”

“…While GFP + grafts from an HH4 PS to an HH4 PS appeared in more anterior (first formed) somites, grafts from an HH8 PS transplanted into HH4 only populated the posterior (later formed) somites. This revealed that the progenitor addition to the PSM is regulated by an intrinsic timer or a definitive prepattern ( Busby et al, 2023 ).…”