RT Journal Article SR Electronic T1 Time-Aligned Hourglass Gastrulation Models in Rabbit and Mouse JF bioRxiv FD Cold Spring Harbor Laboratory SP 2022.11.13.516304 DO 10.1101/2022.11.13.516304 A1 Y Mayshar A1 O Raz A1 S Cheng A1 R Ben-Yair A1 R Hadas A1 N Reines A1 M Mittnenzweig A1 O Ben-Kiki A1 A Lifshitz A1 A Tanay A1 Y Stelzer YR 2022 UL http://biorxiv.org/content/early/2022/11/30/2022.11.13.516304.abstract AB The hourglass model describes the convergence of species within the same phylum to a similar body plan during development, yet the molecular mechanisms underlying this phenomenon in mammals remain poorly described. Here, we compare rabbit and mouse time-resolved differentiation trajectories to revisit this model at single cell resolution. We modeled gastrulation dynamics using hundreds of embryos sampled between gestation days 6.0-8.5, and compare the species using a new framework for time-resolved single-cell differentiation-flows analysis. We find convergence toward similar cell state compositions at E7.5, underlied by quantitatively conserved expression of 76 transcription factors, despite divergence in surrounding trophoblast and hypoblast signaling. However, we observed noticeable changes in specification timing of some lineages, and divergence of primordial germ cells programs, which in the rabbit do not activate mesoderm genes. Comparative analysis of temporal differentiation models provides a new basis for studying the evolution of gastrulation dynamics across mammals.Competing Interest StatementThe authors have declared no competing interest.