The primitive streak and cellular principles of building an amniote body through gastrulation

Description The nonconserved primitive streak In human development, a linear structure called the primitive streak appears 14 days after fertilization. This structure marks the transition of the embryo from having radial to bilateral symmetry. The primitive streak also gives anterior-posterior and dorsal-ventral spatial information to cells undergoing gastrulation and forming the various body cell types. In a Review, Sheng et al. present a phylogenetic and ontogenetic overview of the primitive streak. They discuss organismal, cellular, and molecular features of the primitive streak and how it functions in amniote gastrulation. The observation that this structure is not conserved and is not required for development in vitro has implications for embryonic stem cell–based models and considerations about human development research. —BAP A review details our understanding of the primitive streak during embryonic development: its structure, function, conservation, and more. BACKGROUND Pluripotent cells are generated by embryonic divisions that occur shortly after fertilization. These cells are transformed into the recognizable outline of an organism through the process of gastrulation, which endows them with lineage and spatial identities in the context of an emerging coordinate system. In many amniote embryos (such as those of reptiles, birds, and mammals), gastrulation has been associated with a transient structure called the primitive streak. Human development also follows this pattern. In humans, the primitive streak forms ~14 days after fertilization. The appearance of the primitive streak breaks the radial symmetry of the epiblast (a sheet of epithelialized pluripotent cells) and has been suggested to symbolize the emergence of human individuality. As such, many countries have established a legal limit of 14 days for the in vitro culture of fertilized human eggs—this is known as the “14-day rule. ” In recent years, pluripotent stem cells have become a promising in vitro model for studying the cellular and molecular mechanisms associated with early human development. Interpretation of developmental features observed in these in vitro models requires proper understanding of animal gastrulation in general and of the amniote primitive streak in particular. ADVANCES In this Review, we offer a phylogenetic and ontogenetic overview of the primitive streak and its role in mediating amniote gastrulation, and we discuss the implications of embryonic stem cell–based models of early mammalian embryogenesis on the function of this iconic structure. We provide evidence that the primitive streak is not a conserved feature in amniote development and that the mammalian and avian primitive streaks have evolved independently through different supracellular mechanisms that led to their morphological emergence. We argue that, in addition to mediating the emergence of germ layers from the pluripotent epiblast, gastrulation is principally a process in which an embryo acquires a coordinate system to organize its primary cell fates and the primordia of organs and tissues relative to each other in space. We highlight that in amniotes this process is regulated by a set of conserved signaling and transcriptional networks through a small collection of cellular behaviors, the tissue-level effects of which are governed by boundary conditions. We suggest that changing boundary conditions, in the form of evolution of extraembryonic lineages such as the trophectoderm and primitive endoderm, have played a key role in the transformation of the blastopore, characteristic of anamniote embryos, into the primitive streak. Variability in the organization of these tissues and the demarcation of embryonic and extraembryonic territories underpins the observed variation in the morphological appearance of the primitive streak in mammals and birds and of primitive streak–related structures in reptiles. Over the past few years, embryonic stem cells have been used as models to recapitulate several aspects of early mammalian embryogenesis. These studies have revealed that the germ layers, and even a rudimentary body plan, can form in the absence of a primitive streak. OUTLOOK Our model predicts that the most fundamental feature of a primitive streak–like structure in early amniote development is not its morphological manifestation but rather its capacity to mediate coordinated cell fate specification events in space. Our model also suggests that cell fate specification and tissue-level morphogenesis are regulated independently during gastrulation and then coordinated during embryonic development in vivo. In developmental models in vitro, these two processes can be uncoupled and have been shown to be influenced by different types of biomechanical parameters that mediate their coordination. This modularity leads us to suggest that the in vitro models are useful for studying gastrulation because their use without necessarily having to recapitulate embryonic structures. Future analyses of early amniote development, both in vivo and in vitro, would benefit from putting less emphasis on the primitive streak as a distinct embryological structure and more on its roles as a conduit for symmetry breaking and coordinated germ-layer differentiation. Research into human development has direct societal and ethical impacts. Current ethical oversight in human embryo research, the 14-day rule, is effective in many countries and reflects an interdisciplinary consensus drawn somewhat arbitrarily to determine the legal rights of a human embryo. Our observations suggest that use of the primitive streak as a key developmental landmark for limiting ex vivo culture of human embryos should be reassessed. An alternative landmark, necessary for exerting ethical oversight in human-related developmental and stem cell biology research, should be selected through a consensual discussion between different stakeholders to ensure scientific and ethical rigor. Schematic view of how a human embryo acquires spatial coordination of its primary cell fates through gastrulation. After fertilization, a human embryo implants into the uterus (between days 6 and 12) and gastrulation begins soon afterward, with the primitive streak emerging at day 14. Gastrulation allocates cell fates and spatial coordinates to epiblast cells, laying down the foundation of a human body. Credit: (“Fetus in the womb” sketch) Leonardo Da Vinci/Royal Collection Trust/© Her Majesty Queen Elizabeth II 2021 The primitive streak, a transient embryonic structure, marks bilateral symmetry in mammalian and avian embryos and helps confer anterior-posterior and dorsal-ventral spatial information to early differentiating cells during gastrulation. Its recapitulation in vitro may facilitate derivation of tissues and organs with in vivo–like complexity. Proper understanding of the primitive streak and what it entails in human development is key to achieving such research objectives. Here we provide an overview of the primitive streak and conclude that this structure is neither conserved nor necessary for gastrulation or early lineage diversification. We offer a model in which the primitive streak is viewed as part of a morphologically diverse yet molecularly conserved process of spatial coordinate acquisition. We predict that recapitulation of the primitive streak is dispensable for development in vitro.