Biology subjects

Szekely, P.

Publications and source records attributed to Szekely, P..

4 recordsLinked to original sources

bioRxiv2022

Patterning and growth are coordinated early in the cell cycle

Precise control of cell division is essential for proper patterning and growth during the development of multicellular organisms. Coordination of formative (asymmetric) divisions that generate new tissue patterns with proliferative (symmetric) divisions that promote growth is poorly understood. Here, we employed quantitative 4D light sheet and confocal microscopy to probe in vivo the dynamics of two transcription factors, SHORTROOT (SHR) and SCARECROW (SCR), which are required for asymmetric division in the stem cell niche of Arabidopsis roots [1,2]. Long-term (up to 48 hours), frequent (every 15 minutes) imaging of the two regulators in tandem in single cells, in conjunction with a SHR induction system, enabled us to challenge an existing bistable model[3] of the SHR/SCR gene regulatory network. By directly controlling SHR and SCR expression dynamics, we were able to identify key features that are essential for rescue of asymmetric division in shr mutants. We show that instead of high stable levels of nuclear SHR and SCR, only low transient levels of expression are required. Nuclear SHR kinetics do not follow predictions of the bistable model, and the regulatory relationship between SHR and SCR can be modeled by monostable alternatives. Furthermore, expression of these two regulators early in the cell cycle determines the orientation of the division plane, resulting in either formative or proliferative cell division. Our findings provide evidence for an uncharacterized mechanism by which developmental regulators directly coordinate patterning and growth.

developmental biology↗

bioRxiv2022

Brassinosteroid gene regulatory networks at cellular resolution

Brassinosteroids (BRs) are plant steroid hormones that regulate diverse processes such as cell division and cell elongation. BRs control thousands of genes through gene regulatory networks that vary in space and time. By using time-series single-cell RNA-sequencing to identify BR-responsive gene expression specific to different cell types and developmental stages of the Arabidopsis root, we uncovered the elongating cortex as a site where BRs trigger a shift from proliferation to elongation associated with increased expression of cell wall-related genes. Our analysis revealed HAT7 and GTL1 as BR-responsive transcription factors that regulate cortex cell elongation. These results establish the cortex as an important site for BR-mediated growth and unveil a BR signaling network regulating the transition from proliferation to elongation, illuminating new aspects of spatiotemporal hormone response.

plant biology↗

bioRxiv2018

Universal cancer tasks, evolutionary tradeoffs, and the functions of driver mutations

Recent advances have led to an appreciation of the vast molecular diversity of cancer. Detailed data has enabled powerful methods to sort tumors into groups with benefits for prognosis and treatment. We are still missing, however, a general theoretical framework to understand the diversity of tumor gene-expression and mutations. To address this, we present a framework based on multi-task evolution theory, using the fact that tumors evolve in the body, and that tumors are faced with multiple tasks that contribute to their fitness. In accordance with the theory, we find that tradeoff between tasks constrains tumor gene-expression to a continuum bounded by a polyhedron. The vertices of the polyhedron are gene-expression profiles each specializing in one task, allowing the tasks to be identified. We find five universal cancer tasks across tissue-types: cell-division, biomass & energy, lipogenesis, immune-interaction and invasion & tissue remodeling. Tumors whose gene-expression lies close to a vertex are task specialists. We find evidence that such specialists are more sensitive to drugs that interfere with this task. We find that driver mutations, but not passenger mutations, tune gene-expression towards specialization in specific tasks. This approach can integrate additional types of molecular data into a theoretically-based framework for understanding tumor diversity.

cancer biology↗

bioRxiv2018

Evolutionary tradeoffs and the structure of allelic polymorphisms

Populations of organisms show prevalent genetic differences called polymorphisms. Understanding the effects of polymorphisms is of central importance in biology and medicine. Here, we ask which polymorphisms occur at high frequency when organisms evolve under tradeoffs between multiple tasks. Multiple tasks present a problem, because it is not possible to be optimal at all tasks simultaneously and hence compromises are necessary. Recent work indicates that tradeoffs lead to a simple geometry of phenotypes in the space of traits: phenotypes fall on the Pareto front, which is shaped as a polytope: a line, triangle, tetrahedron etc. The vertices of these polytopes are the optimal phenotypes for a single task. Up to now, work on this Pareto approach has not considered its genetic underpinnings. Here, we address this by asking how the polymorphism structure of a population is affected by evolution under tradeoffs. We simulate a multi-task selection scenario, in which the population evolves to the Pareto front: the line segment between two archetypes or the triangle between three archetypes. We find that polymorphisms that become prevalent in the population have pleiotropic phenotypic effects that align with the Pareto front. Similarly, epistatic effects between prevalent polymorphisms are parallel to the front. Alignment with the front occurs also for asexual mating. Alignment is reduced when drift or linkage is strong, and is replaced by a more complex structure in which many perpendicular allele effects cancel out. Aligned polymorphism structure allows mating to produce offspring that stand a good chance of being optimal multi-taskers in at least one of the locales available to the species.

systems biology↗