Size-reduced embryos reveal a gradient scaling based mechanism for zebrafish somite formation

Abstract

Little is known about how the sizes of animal tissues are controlled. A prominent example is somite size, which varies widely both within an individual and across species. Despite intense study of the segmentation clock governing the timing of somite generation, how it relates to somite size is poorly understood. Here, we examine somite scaling and find that somite size at specification scales with the length of the presomitic mesoderm (PSM) despite considerable variation in PSM length across developmental stages and in surgically size-reduced embryos. Measurement of clock period, axis elongation speed and clock gene expression patterns demonstrate that existing models fail to explain scaling. We posit a 'clock and scaled gradient' model, in which somite boundaries are set by a dynamically scaling signaling gradient across the PSM. Our model not only explains existing data, but also makes a unique prediction that we confirm experimentally - the formation of periodic 'echoes' in somite size following perturbation of the size of one somite. Our findings demonstrate that gradient scaling plays a central role in both progression and size control of somitogenesis.

From local resynchronization to global pattern recovery in the zebrafish segmentation clock

“…It is possible that a quantitative description should also take the phenomenon of changing segment length into account. This would require a timelapse analysis of the forming segments during perturbations and a greater understanding of the mechanism underlying the determination of and change in segment lengths during development(55,56), and could be accommodated in the framework of the current model. In summary, the formulation of the model allows a quantitative comparison to experimental data and a phenomenological understanding of pattern recovery.Vortices could arise in other models of the segmentation clock with similar local interactions(28,34,35,57).…”

“…In addition, this result implies that the quantification of global tissue parameters will be necessary to obtain quantitative agreement between theory and experiment. Temporal changes in PSM length have been measured in various species(5,6,55), and cell advection patterns across the PSM have been investigated(8)(9)(10)71). Involvement of these global tissue properties discriminates the resynchronization of the segmentation clock from its desynchronization, which is dominated by local cellular properties such as noise in clock gene expression(18,19,23,72).Furthermore, morphological tissue development distinguishes the synchronization of the segmentation clock from that of other biological oscillator systems in spatially static tissues, such as the suprachiasmatic nucleus in the mammalian circadian clock (73).…”

Scaling of submicrometric Turing patterns in concentrated growing systems

“…The proposed scenario, involving a strengthening of molecular crowding in smaller embryos, could be considered to support the observed scaling of spatial structures in biology, for example, the adaptation of somite size to embryo size and, more generally, the preservation of proportions in morphogenesis [48]. The results give some hints to design a chemical scheme enabling the formation of a tailored Turing pattern in mesocale chemical engineering.…”

“…(38) in the form z 4 + pz 2 + qz + r = 0 (48) It is sufficient to find a root of the third equation: 8y 3 − 4py 2 − 8ry + 4pr − q 2 = 0 (49) to find the roots of Eq. (48). Following Cardan method [49], we introduce…”

Constraints on somite formation in developing embryos

“…By steady state, we do not mean that ϕ ( x ) is time independent, but rather that ϕ ( x ) is the same, modulo 2 π , at corresponding times between somite formation (for example, right before, or right after, a somite forms). This means that the phase profile exhibits what has been termed ‘dynamical scaling’ in the literature [22], i.e. as the PSM changes in length the pattern of oscillations across it scales correspondingly.…”