title: Scaling of embryonic patterning based on phase-gradient encoding.
abstract: A fundamental feature of embryonic patterning is the ability to scale and maintain stable proportions despite changes in overall size, for instance during growth. 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. Despite decades of experimental and theoretical work, the underlying mechanism remains unknown. More recently, ultradian oscillations in gene activity have been linked to the temporal control of segmentation; 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.
authors.affiliation: Developmental Biology Unit, European Molecular Biology Laboratory, 69117 Heidelberg, Germany.
authors.forename: Volker M
authors.initials: VM
authors.lastname: Lauschke
authors.forename: Charisios D
authors.initials: CD
authors.lastname: Tsiairis
authors.forename: Paul
authors.initials: P
authors.lastname: François
authors.forename: Alexander
authors.initials: A
authors.lastname: Aulehla
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000502:physiology*; D049628:Body Size; D002478:Cells, Cultured; D003463:Cues; D004622:Embryo, Mammalian / Q000033:anatomy & histology* / Q000166:cytology / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental; D066298:In Vitro Techniques; D008648:Mesoderm / Q000033:anatomy & histology* / Q000166:cytology / Q000196:embryology*; D051379:Mice; D008954:Models, Biological; D013696:Temperature