biostudies-literatureUnknownSong YHow developmental timings are regulated is a fundamental open question. Two widely considered mechanisms are the clock, in which an internal timer determines when each stage occurs, and the domino, in which the completion of each stage triggers the next. It is often unclear how to establish either mechanism. Here, we construct a quantitative framework that uses the correlation structure of developmental timings to test the clock and domino mechanisms. We apply this framework to human pre-implantation development by using ~1 million images of 2946 embryos acquired during IVF treatment, establishing mathematical models of developmental rate. We find that a domino mechanism governs the cleavage timings, while a pronuclei fade-triggered clock mechanism governs the morula and blastocyst timingsbioRxiv : the preprint server for biology2026.01.25.701537https://www.ebi.ac.uk/biostudies/studies/S-EPMC12874018biostudies-literatureClocks and Dominoes: Timing Mechanisms of Embryogenesis.PMC12874018Pfister HBen-Yosef DNeedleman DJLeahy BDSong YfalseClocks and Dominoes: Timing Mechanisms of Embryogenesis.How developmental timings are regulated is a fundamental open question. Two widely considered mechanisms are the clock, in which an internal timer determines when each stage occurs, and the domino, in which the completion of each stage triggers the next. It is often unclear how to establish either mechanism. Here, we construct a quantitative framework that uses the correlation structure of developmental timings to test the clock and domino mechanisms. We apply this framework to human pre-implantation development by using ~1 million images of 2946 embryos acquired during IVF treatment, establishing mathematical models of developmental rate. We find that a domino mechanism governs the cleavage timings, while a pronuclei fade-triggered clock mechanism governs the morula and blastocyst timings2026-01-01T00:00:00Z2026 Jan2026-07-09T11:53:20.858Z2026-07-09T11:02:49.428ZS-EPMC128740184165941510.64898/2026.01.25.701537