Spatiotemporal Frameworks of Morphogenesis and Cell Lineage Specification in Pre- and Peri-Implantation Mammalian Embryogenesis: Insights and Knowledge Gaps from Mouse Embryo

Research on mammalian embryogenesis has been revolutionised by rapid technological and methodological advancements. This review seeks to synthesise historical and contemporary studies on mouse embryos to provide comprehensive conceptual frameworks of early embryogenesis. Key research findings from live-cell imaging, fluorescence staining, molecular, and sequencing analyses were reassessed, mainly focusing on in vivo and in vitro mouse embryo models. Through critical reassessment, this review first presents historical progress in mammalian models and culture systems for the study of embryogenesis. Subsequently, it elucidates the spatiotemporal progression of morphological events from pre- to peri-implantation across tissue, cellular, and molecular scales. The critical analysis in this review highlights that prevailing and alternative models for pre-implantation cell lineage specification are not mutually exclusive but, rather, describe complementary aspects of embryogenesis. While multiple factors in peri-implantation cell lineage specification are discussed, establishing integrative theoretical models requires further investigation into the crosstalk between different factors during lineage decision-making. Furthermore, this work identifies that precise spatiotemporal dynamics and mechanisms, particularly those governing the initiation, progression, and maintenance of morphological and lineage decisions, remain major knowledge gaps. Lastly, this review provides critical thinking frameworks for assessing current models and defining specific experimental pathways to address enduring unresolved knowledge gaps regarding early embryogenesis.