It takes a village to form embryo models

How do cells orchestrate growth and forms? New entry points into this classical question have emerged through the formation of embryo models made solely from stem cells. These models are more scalable, versatile, and accessible than mammalian embryos, opening up new avenues for investigating knowledge gaps in embryogenesis and organogenesis (see in this issue Rossant and Tam, 1031). Understanding the basic principles of proliferation, differentiation, patterning, and morphogenesis not only fulfills our curiosity but also settles ground rules for tissue engineering, regenerative medicine, and disease modeling (see in this issue Moris et al., 1021). Embryo models are especially relevant for species whose development is poorly understood due to inaccessibility, scarcity, or ethical status. This is particularly true for mammalians, including humans, and non-model organisms, including rare species. Although embryo models were initially developed using mouse and human stem cells, this field can extend to other species, broadening the space for discoveries about the ‘‘endless formsmost beautiful and most wonderful,’’ as described by Charles Darwin. The origin of embryo models can be traced back to embryoid bodies, aggregates of pluripotent stem cells undergoing lineage specification, which proved very useful for validating their differentiation potential. However, embryoid bodies form rather disorganized tissues, which prevents developmental progression. This limitation prompted efforts from Yoshiki Sasai and others in more finely directing pluripotent stem cells to recapitulate aspects of organogenesis. Continuing in this vein, embryo models are generated by combining pluripotent stem cells, sometimes along with extraembryonic stem cells, in precisely controlled numbers, geometries, and physicochemical environments mimicking developmental cues. This triggers cells to re-enact aspects of embryogenesis reflecting the formation of the pre-implantation blastocyst and postimplantation gastrula, all the way to early organogenesis including the development of the nervous system and the heart (Figure 1). Self-organization. Embryogenesis has historically been viewed through the lens of pre-patterning, whether by local deposition of maternal RNA or by mechanochemical inductions often originating from extraembryonic tissues. This knowledge of embryonic-extraembryonic interactions has been repurposed to form embryo models and tissue decoupling of has refined our understanding of inductions. It has also highlighted a certain level of tissue autonomy and arguably underappreciated processes of self-