Shaping Organs: Shared Structural Principles Across Kingdoms.

Development encapsulates the morphogenesis of an organism from a single fertilized cell to a functional adult. A critical part of development is the specification of organ forms. Beyond the molecular control of morphogenesis, shape in essence entails structural constraints and thus mechanics. Revisiting recent results in biophysics and development, and comparing animal and plant model systems, we derive key overarching principles behind the formation of organs across kingdoms. In particular, we highlight how growing organs are active rather than passive systems and how such behavior plays a role in shaping the organ. We discuss the importance of considering different scales in understanding how organs form. Such an integrative view of organ development generates new questions while calling for more cross-fertilization between scientific fields and model system communities.

Shaping the zebrafish myotome by intertissue friction and active stress.

Organ formation is an inherently biophysical process, requiring large-scale tissue deformations. Yet, understanding how complex organ shape emerges during development remains a major challenge. During zebrafish embryogenesis, large muscle segments, called myotomes, acquire a characteristic chevron morphology, which is believed to aid swimming. Myotome shape can be altered by perturbing muscle cell differentiation or the interaction between myotomes and surrounding tissues during morphogenesis. To disentangle the mechanisms contributing to shape formation of the myotome, we combine single-cell resolution live imaging with quantitative image analysis and theoretical modeling. We find that, soon after segmentation from the presomitic mesoderm, the future myotome spreads across the underlying tissues. The mechanical coupling between the future myotome and the surrounding tissues appears to spatially vary, effectively resulting in spatially heterogeneous friction. Using a vertex model combined with experimental validation, we show that the interplay of tissue spreading and friction is sufficient to drive the initial phase of chevron shape formation. However, local anisotropic stresses, generated during muscle cell differentiation, are necessary to reach the acute angle of the chevron in wild-type embryos. Finally, tissue plasticity is required for formation and maintenance of the chevron shape, which is mediated by orientated cellular rearrangements. Our work sheds light on how a spatiotemporal sequence of local cellular events can have a nonlocal and irreversible mechanical impact at the tissue scale, leading to robust organ shaping.

Spatiotemporal sensitivity of mesoderm specification to FGFR signalling in the Drosophila embryo.

Development of the Drosophila embryonic mesoderm is controlled through both internal and external inputs to the mesoderm. One such factor is Heartless (Htl), a Fibroblast Growth Factor Receptor (FGFR) expressed in the mesoderm. Although Htl has been extensively studied, the dynamics of its action are poorly understood after the initial phases of mesoderm formation and spreading. To begin to address this challenge, we have developed an optogenetic version of the FGFR Heartless in Drosophila (Opto-htl). Opto-htl enables us to activate the FGFR pathway in selective spatial (~ 35 µm section from one of the lateral sides of the embryo) and temporal domains (ranging from 40 min to 14 h) during embryogenesis. Importantly, the effects can be tuned by the intensity of light-activation, making this approach significantly more flexible than other genetic approaches. We performed controlled perturbations to the FGFR pathway to define the contribution of Htl signalling to the formation of the developing embryonic heart and somatic muscles. We find a direct correlation between Htl signalling dosage and number of Tinman-positive heart cells specified. Opto-htl activation favours the specification of Tinman positive cardioblasts and eliminates Eve-positive DA1 muscles. This effect is seen to increase progressively with increasing light intensity. Therefore, fine tuning of phenotypic responses to varied Htl signalling dosage can be achieved more conveniently than with other genetic approaches. Overall, Opto-htl is a powerful new tool for dissecting the role of FGFR signalling during development.

The cell-free translation of Rauscher leukemia virus RNA into high molecular weight polypeptides.

Rauscher leukemia virus (RLV) 65-S RNA, 35-S mengovirus RNA and reticulocyte A-rich RNA each stimulated cell-free protein synthesis in a JLS-V5 cell derived S-30 system. rRNA, however, was not stimulatory in this system. Of the stimulated protein products only those synthesized in response to added RLV RNA were immune-precipitable with anti-RLV rabbit serum. Furthermore, cell-free incubations with pactamycin at a concentration which specifically inhibits initiation and not elongation prevented the stimulation of amino acid incorporation in response to added RLV RNA. Analysis of the polypeptides synthesized by the cell-free system in response to reticulocyte A-rich RNA, showed them to be globin-like and, therefore, also mRNA specific. The RLV RNA-directed product included at least two classes of polypeptides (mol. wts of 140 000-185 000 and 50 000-75 000) both of which were larger than the group specific polypeptides of mature virions. None of the internal structural polypeptides of mature virions were synthesized in response to RLV RNA. The large molecular weight, viral-specific polypeptides are candidate precursor polyproteins which may represent the translational products of a polycistronic mRNA with a single initiation site.

Spin freezing in geometrically frustrated antiferromagnets with weak disorder.

We investigate the consequences for geometrically frustrated antiferromagnets of weak disorder in the strength of exchange interactions. Taking as a model the classical Heisenberg antiferromagnet with nearest neighbor exchange on the pyrochlore lattice, we examine low-temperature behavior. We show that spatial modulation of exchange generates long-range effective interactions within the extensively degenerate ground states of the clean system. Using Monte Carlo simulations, we find a spin glass transition at a temperature set by the disorder strength. Disorder of this type, which is generated by random strains in the presence of magnetoelastic coupling, may account for the spin freezing observed in many geometrically frustrated magnets.