Self-organization in embryonic development: myth and reality

Self-organization has become a watchword in developmental biology, characterizing observations in which embryonic or induced stem cells replicate morphological steps and outcomes seen in intact embryos. While the term was introduced in the 18th century by the philosopher Immanuel Kant to describe the goal-directed properties of living systems, it came into modern use for non-living materials in which complex forms and patterns emerge through dynamical, energy-expending physical processes. What are the relationships among these uses of the term? While multicellular forms arose dozens of times from single-celled organisms, only some of these undergo development, and not all developmental processes are self-organizing. The evolution of the animals (metazoans) from unicellular holozoans was accompanied by the addition of novel gene products which mediated the constitution of the resulting cell clusters as liquid-, liquid crystal-, and solid-like materials with protean morphogenetic propensities. Such materials variously exhibited multilayering, lumen formation and elongation, echoing the self-organizing properties of nonliving matter, generic based on such parallels, though with biologically based subunit properties and modes of interaction. These effects provided evolutionary templates for embryonic forms and morphological motifs of diverse metazoan lineages. Embryos and organ primordia of present-day animal species continue to generate forms that resemble the outcomes of these physical effects. Their development, however, employs overdetermined, highly evolved mechanisms that are often disconnected from their originating processes. Using the examples of gastrulation, somitogenesis, and limb skeletal development, this chapter provides instances of, and a conceptual framework for understanding, the relationships between physical and evolved types of developmental self-organization.

Cell differentiation: what have we learned in 50 years?

I revisit two theories of cell differentiation in multicellular organisms published a half-century ago, Stuart Kauffmans global gene regulatory dynamics (GGRD) model and Roy Brittens and Eric Davidsons modular gene regulatory network (MGRN) model, in light of newer knowledge of mechanisms of gene regulation in the metazoans (animals). The two models continue to inform hypotheses and computational studies of differentiation of lineage-adjacent cell types. However, their shared notion (based on bacterial regulatory systems) of gene switches and networks built from them, have constrained progress in understanding the dynamics and evolution of differentiation. Recent work has described unique write-read-rewrite chromatin-based expression encoding in eukaryotes, as well metazoan-specific processes of gene activation and silencing in condensed-phase, enhancer-recruiting regulatory hubs, employing disordered proteins, including transcription factors, with context-dependent identities. These findings suggest an evolutionary scenario in which the origination of differentiation in animals, rather than depending exclusively on adaptive natural selection, emerged as a consequence of a type of multicellularity in which the novel metazoan gene regulatory apparatus was readily mobilized to amplify and exaggerate inherent cell functions of unicellular ancestors. The plausibility of this hypothesis is illustrated by the evolution of the developmental role of Grainyhead-like in the formation of epithelium.