Journal Article

Scaling of embryonic patterning based on phase-gradient encoding

Tsiairis, Charisios D., Aulehla, Alexander, Lauschke, Volker M., François, Paul

2013

Overview

An ex vivo primary culture assay is developed that recapitulates mouse embryonic mesodermal patterning and segment formation; using this approach, it is shown that oscillating gene activity is central to maintain stable proportions during development. Embryo scaling via oscillating genes How does a developing organism maintain its proportions as it grows? The process is termed scaling, but it is little understood. This paper describes a novel model in which to address this fundamental problem in biology: an ex vivo mouse mesoderm cell culture in a Petri dish in which mesodermal patterning and segment formation take place, complete with scaling. Using this approach, the authors found that the embryo uses periodic (oscillating) gene activity to maintain its proportions. This periodic gene activity responds to changes in overall embryo size and in turn controls the formation of embryo structures. A fundamental feature of embryonic patterning is the ability to scale and maintain stable proportions despite changes in overall size, for instance during growth 1 , 2 , 3 , 4 , 5 , 6 . A notable example occurs during vertebrate segment formation: after experimental reduction of embryo size, segments form proportionally smaller, and consequently, a normal number of segments is formed 1 , 7 , 8 . Despite decades of experimental 1 , 7 and theoretical work 9 , 10 , 11 , the underlying mechanism remains unknown. More recently, ultradian oscillations in gene activity have been linked to the temporal control of segmentation 12 ; however, their implication in scaling remains elusive. Here we show that scaling of gene oscillation dynamics underlies segment scaling. To this end, we develop a new experimental model, an ex vivo primary cell culture assay that recapitulates mouse mesoderm patterning and segment scaling, in a quasi-monolayer of presomitic mesoderm cells (hereafter termed monolayer PSM or mPSM). Combined with real-time imaging of gene activity, this enabled us to quantify the gradual shift in the oscillation phase and thus determine the resulting phase gradient across the mPSM. Crucially, we show that this phase gradient scales by maintaining a fixed amplitude across mPSM of different lengths. We identify the slope of this phase gradient as a single predictive parameter for segment size, which functions in a size- and temperature-independent manner, revealing a hitherto unrecognized mechanism for scaling. Notably, in contrast to molecular gradients, a phase gradient describes the distribution of a dynamical cellular state. Thus, our phase-gradient scaling findings reveal a new level of dynamic information-processing, and provide evidence for the concept of phase-gradient encoding during embryonic patterning and scaling.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/136/756/1640 / 631/1647/1407 / Allometry / Animals / Biological and medical sciences / Body Patterning - physiology / Body Size / Cell culture / Cells, Cultured / Cleavage (Embryology) / Cues / Embryo, Mammalian - anatomy & histology / Embryo, Mammalian - cytology / Embryo, Mammalian - embryology / Embryology: invertebrates and vertebrates. Teratology / Embryonic development / Fundamental and applied biological sciences. Psychology / Gene Expression Regulation, Developmental / Genetic aspects / Humanities and Social Sciences / In Vitro Techniques / letter / Mesoderm - anatomy & histology / Mesoderm - cytology / Mesoderm - embryology / Mice / Models, Biological / multidisciplinary / Observations / Organogenesis. Fetal development / Organogenesis. Physiological fonctions / Science / Temperature / Vertebrates