ABSTRACTS CELL BIOLOGY 4 ANNUAL MEETING FLORENCE 2018 CELL BIOLOGY ABSTRACTS 276 C1 SYSTEMS ANALYSES OF MULTICELLULARITY COMPLEXITY AND ORGAN BIOLOGY ORGANISED BY: GEORGE BASSEL (UNIVERSITY OF BIRMINGHAM, UK), LEAH BAND (UNIVERSITY OF NOTTINGHAM, UK) AND MARK FRICKER (UNIVERSITY OF OXFORD, UK) which subtle heterogeneities can disrupt epithelial development. C1.1 THE MORPHOSPACE OF SYNTHETIC At t he cel lu la r level, t he i n flue nce of d i ffe re nt ia l cel l si ze on epit hel ial MULICELLULARITY order is poorly understood. By altering epithelial cell size through genetic perturbations in clonal populations, we demonstrate that changes in relative apical surface area can predictably destabilize WEDNESDAY 4 JULY, 2018 10:30 cell-cell junctions in developing Drosophila wing discs. These changes in cell junctions in turn disrupt clonal contiguity and drive a RICARD SOLÉ (POMPEU FABRA UNIVERSITY, SPAIN) stereotyped reorganization of local epithelial topology. Separately, I will describe a genetic technique that allows for the generation of [email protected] heterozygous cell clones in v ivo. Using this system, I will propose the concept of deleterious heteromosaicism, whereby mutant Multicellularity is a crucial innovation that has taken place alleles that are recessive and completely viable in heterozygotes independently at least 25 times in the evolution of life on our planet. can nevertheless elicit deleterious phenotypes when present in Uncovering the evolutionary rules associated to the emergence of heterozygous cell clones. this transition has been partially achieved thanks to a combination of comparative cell biology, phylogenetic, palaeobiology and genomic studies of primitive model organisms. An alternative path to this goal is the use of synthetic and systems approximations C1.3 TRANSPORT AND COMMUNICATION including both experimental and mathematical models. An IN BODY PLANS: ARCHITECTURAL ambitious research programme should consider not only those aspects related to genetic regulatory networks and the conditions CONSTRAINTS DUE TO DIMENSIONALITY for the emergence of developmental plans and life cycles, but also crucial aspects associated to the environmental context. In this WEDNESDAY 4 JULY, 2018 11:30 presentation we will explore several key results, formulate a list of open problems and suggest potentially relevant avenues to follow SALVA DURAN-NEBREDA (UNIVERSITY OF BIRMINGHAM, UNITED at the crossroads between ecology, evolution and development. KINGDOM), GEORGE BASSEL (UNIVERSITY OF BIRMINGHAM, UNITED KINGDOM) [email protected] C1.2 TO P O LO GY, G E O M E TRY, CLONALITY: THE FUNDAMENTAL Over the course of multicellular evolution several key innovations have occurred that fundamentally changed the design space and CONSTRAINTS ON EPITHELIAL ORDER dimensionality of body plans for plants, animals and fungi. From filamentous organisms to fractal geometries to 2D sheets to 3D WEDNESDAY 4 JULY, 2018 11:00 structures and finally the invention of specialized tissues for transport (vasculature). Each of these transitions allowed for the exploration MATT GIBSON (STOWERS INSTITUTE FOR MEDICAL RESEARCH, of new design spaces, further organismal complexity to be achieved UNITED STATES), SUBU RAMANATHAN (STOWERS INSTITUTE FOR a nd establ i shed profou nd mod i ficat ion s to t he mode of t ra n spor t a nd MEDICAL RESEARCH, UNITED STATES), TAK AKIYAMA (STOWERS communication in these organisms. Here we propose a framework INSTITUTE FOR MEDICAL RESEARCH, UNITED STATES) to understand such transitions in terms of topological distances in cellular contact networks. This framework shows that each of these [email protected] transitions fundamentally changes the scaling properties of the organism/organ graphs, i.e. the mathematical relationship between Conserved principles underlying epithelial organization have average path length and organism size. This suggests that each emerged over the last several decades, though most of our knowledge transition allowed for bigger organisms to exist while maintaining is restricted to studies on homogenous cell sheets. Here I will discuss similar average path length distances, transcending the topological two ongoing projects that touch on different mechanisms by limitations of the previous architectures. ANNUAL MEETING FLORENCE 2018 CELL BIOLOGY ABSTRACTS 277 C1.4 DETERMINING THE RULES C1.6 TWO MECHANISMS FOR FOR SELF-ORGANISED ADAPTIVE REGULATING DIRECTIONAL GROWTH OF BIOLOGICAL NETWORKS CELLS IN LATERAL ROOTS WEDNESDAY 4 JULY, 2018 11:45 WEDNESDAY 4 JULY, 2018 12:30 MARK FRICKER (UNIVERSITY OF OXFORD, UNITED KINGDOM) CHARLOTTE E M KIRCHHELLE (UNIVERSITY OF OXFORD, UNITED KINGDOM), DANIEL GARCÍA-GONZALEZ (UNIVERSITY OF [email protected] OXFORD, UNITED KINGDOM), ANTOINE JÉRUSALEM (UNIVERSITY OF OXFORD, UNITED KINGDOM), IAN MOORE (UNIVERSITY OF Fungi form extensive interconnected mycelial networks that OXFORD, UNITED KINGDOM) scavenge e ffic ient ly for sca rce resou rces i n a patc hy env i ron ment, in the face of competition and predation. Exploration, repair and combat [email protected] require internal transport of nutrients from spatially disparate sources Multicellular plants robustly and reproducibly generate organs of to these rapidly altering sinks. Thus, the network architecture and astonishing morphological diversity. As plant cells are encased i nte r na l flows cont i nuou sly adapt to loca l nut r it iona l c ues, da mage by a rigid cell wall and cannot migrate from their position in the or predation, through growth, branching, fusion or regression. As tissue, this diversity in shape depends on the plant’s ability to these organisms do not have any centralised control system, we establish and precisely control directional cell growth. Cell growth infer their relatively sophisticated behaviour emerges from parallel occurs principally perpendicular to the net direction of cellulose implementation of many local decisions that collectively manage to m icrofibr i ls i n t he cel l wa l l. Th is is i n tu r n cont rol led by cor t ica l solve this complex, dynamic combinatorial optimisation problem. microtubule orientation, which guide trajectories of cellulose To understand how such behaviour is achieved and coordinated, synthase complexes as new cellulose is laid down. In young lateral we have developed combined imaging and modelling approaches to roots of Arabidopsis thaliana, growth anisotropy is also dependent characterise the network structure, link the structure to predicted on RAB-A5c, a plant-specific small GTPase that specifies an nut r ient t ra n spor t, ba sed on models of flu id flow dy na m ics, a nd t he n e ndome mbra ne t ra ffic k i ng pat hway to t he geomet r ic edges of cel l s. test t hese pred ic t ion s u si ng mea su re me nt of nut r ie nt flows u si ng Here we investigate the relationship between cortical microtubule photon-counting scintillation imaging. In parallel, we have explored organisation and RAB-A5c action at geometric edges during lateral control of network development in the acellular slime mold, Physarum root morphogenesis. We show that RAB-A5c associates with cortical polycephalum, which is taxonomically unrelated to the fungi, yet m ic rot ubu les at cel l edges, wh ic h a re necessa r y but i n su ffic ie nt to appears to exemplify common solutions to self-organised adaptive explain RAB-A5c distribution at individual cell edges. Importantly, network formation driven by fluid flows, local rules and oscillatory when RAB-A5c is inhibited, loss of longitudinal growth anisotropy behaviour. The simplicity of the bioinspired Physarum model hints at a is associated with increased rather than reduced anisotropy class of algorithms that give quasi-optimal solutions to balancing cost of cortical microtubules in transverse orientation. We present and transport efficiency using a combination of iterative local rules genetic, pharmacological, and modelling evidence that formation with long-range coupling. By adopting a comparative approach across of anisotropic cortical microtubule arrays partially compensates widely divergent organisms, we aim to identify universal biological for loss of an independent RAB-A5c-mediated mechanism that algorithms that yield optimised network design. maintains anisotropic growth in meristematic cells. C1.5 HIGHER-ORDER ORGANIZATION OF C1.7 DATA-DRIVEN MODELLING: CELLS IN THE SHOOT APICAL MERISTEM IDENTIFYING CELLULAR BEHAVIOURS DRIVING REGENERATIVE GROWTH WEDNESDAY 4 JULY, 2018 12:15 GEORGE BASSEL (UNIVERSITY OF BIRMINGHAM, WEDNESDAY 4 JULY, 2018 15:00 UNITED KINGDOM) FABIAN ROST (MAX PLANCK INSTITUTE FOR THE PHYSICS OF [email protected] COMPLEX SYSTEMS, GERMANY) Self-organization in multicellular systems is the product of cell cycle [email protected] control and positioning of cells within organs. Local geometric and The salamander axolotl, A . mexicanum, is unique in its ability to topological rules predicting the timing and location of cell divisions regenerate a fully functional tail after amputation. We aimed to have bee n desc r ibed prev iou sly i n pla nt s a nd a n i ma l s. We ide nt i fied identify the cellular behaviours driving the re-growth of the spinal a simple mathematical rule that uses the position of a cell within the cord tissue. Cellular behaviours that could drive tissue growth are global context of a plant shoot apical meristem to predict each cell cell division, movement, differentiation, cell death as well as cell cycle induction and cell division placement. This network-based shape a nd si ze c ha nges. We combi ned i mage qua nt i ficat ion a nd analyses of cellular resolution self-organization dynamics revealed data-driven models to quantify all relevant cellular behaviours. global path length is maximized within the plant shoot apex. Cells Taking a mathematical modelling approach, we integrated these which lie upon shorter paths therefore have a greater propensity to qua nt i ficat ion s to show t hat t he accele rat ion of t he cel l c yc le i s t he divide, and the placement of subsequent cell division planes in turn major driver of regenerative growth in the axolotl spinal cord.