Figure 4.

Sequential pattern formation in developmental systems. (a) In in vitro cultured neurones, polarity arises sequentially. A second polarity axis is formed after cell growth, and its orientation is “mirrored” off the first. A putative symmetry breaking circuit is presented adjacently [69], considering a membrane-protein (MP) activator coupled to modulators of endocytosis (ME), representing the effects of small GTPases. (b) Gastruloids polarise and elongate only when initialised with a critical number of cells [70]. For seed numbers beyond this initial bifurcation value, gastruloids can self-organise more axes. T/Brachyury expression is localised to the protrusion in monopolarised gastruloids, and is speculated to also be localised to further protrusions in multipolar variants. A potential feedback circuit is drawn adjacently, which remains to be investigated. (c) An activator–substrate model for lung branching [25], based on autocatalytic production of the signalling molecule Shh (activator) at the lung bud tip, via consumption of the substrate molecule Fgf10. (d) A dot-stripe mechanism is proposed to pattern the joints of developing digits: a Turing-like dot-forming system specifies the positions of bones and orients through repression a Turing-like stripe-forming system to specify joints. Modelled on a growing domain, sequential joint specification emerges, with joints forming near the developing tip. A coupled Turing scheme is described adjacent, considering a dot-forming substrate-depletion module (A,S) coupled to a stripe-forming activator–inhibitor module (B,I).