Publications

Behavioral circadian rhythms are controlled by multi-oscillator networks comprising functionally different subgroups of clock neurons. Studies have demonstrated that molecular clocks in the fruit fly Drosophila melanogaster are regulated differently in clock neuron subclasses to support their specific functions (Lee et al., 2016; Top et al., 2016). The nuclear receptor unfulfilled (unf) represents a regulatory node that provides the small ventral Lateral Neurons (s-LNvs) unique characteristics as the master pacemaker (Beuchle et al., 2012). We previously showed that UNF interacts with the s-LNv molecular clocks by regulating transcription of the core clock gene period (per) (Jaumouille et al., 2015). To gain more insight into the mechanisms by which UNF contributes to the functioning of the circadian master pacemaker, we identified UNF target genes using chromatin immunoprecipitation. Our data demonstrate that a previously uncharacterized gene CG7837, which we termed R and B (Rnb), acts downstream of UNF to regulate the function of s-LNvs as the master circadian pacemaker. Mutations and LNv-targeted adult-restricted knockdown of Rnb impair locomotor rhythms. RNB localizes to the nucleus and its loss-of-function blunts the molecular rhythms and output rhythms of the s-LNvs, particularly the circadian rhythms in PDF accumulation and axonal arbor remodeling. These results establish a second pathway by which UNF interacts with the molecular clocks in the s-LNvs and highlight the mechanistic differences in the molecular clockwork within the pacemaker circuit.SIGNIFICANCE STATEMENTCircadian behavior is generated by a pacemaker circuit comprising diverse classes of pacemaker neurons, each of which contains a molecular clock. In addition to the anatomical and functional diversity, recent studies have shown the mechanistic differences in the molecular clockwork among the pacemaker neurons in Drosophila Here, we identified the molecular characteristics distinguishing the s-LNvs, the master pacemaker of the locomotor rhythms, from other clock neuron subtypes. We demonstrated that a newly identified gene Rnb is a s-LNv-specific regulator of the molecular clock and essential for the generation of circadian locomotor behavior. Our results provide additional evidence to the emerging view that the differential regulation of the molecular clocks underlies the functional differences among the pacemaker neuron subgroups.

Kainate receptors (KARs) consist of a class of ionotropic glutamate receptors, which exert diverse pre- and postsynaptic functions through complex signaling regulating the activity of neural circuits. Whereas numerous small-molecule positive allosteric modulators of the ligand-binding domain of (S)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propanoic acid (AMPA) receptors have been reported, no such ligands are available for KARs. In this study, we investigated the ability of three benzothiadiazine-based modulators to potentiate glutamate-evoked currents at recombinantly expressed KARs. 4-cyclopropyl-7-fluoro-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide (BPAM344) potentiated glutamate-evoked currents of GluK2a 21-fold at the highest concentration tested (200 μM), with an EC50 of 79 μM. BPAM344 markedly decreased desensitization kinetics (from 5.5 to 775 ms), whereas it only had a minor effect on deactivation kinetics. 4-cyclopropyl-7-hydroxy-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide (BPAM521) potentiated the recorded peak current amplitude of GluK2a 12-fold at a concentration of 300 μM with an EC50 value of 159 μM, whereas no potentiation of the glutamate-evoked response was observed for 7-chloro-4-(2-fluoroethyl)-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide (BPAM121) at the highest concentration of modulator tested (300 μM). BPAM344 (100 μM) also potentiated the peak current amplitude of KAR subunits GluK3a (59-fold), GluK2a (15-fold), GluK1b (5-fold), as well as the AMPA receptor subunit GluA1i (5-fold). X-ray structures of the three modulators in the GluK1 ligand-binding domain were determined, locating two modulator-binding sites at the GluK1 dimer interface. In conclusion, this study may enable the design of new positive allosteric modulators selective for KARs, which will be of great interest for further investigation of the function of KARs in vivo and may prove useful for pharmacologically controlling the activity of neuronal networks.

Animal cell shape is largely determined by the cortex, a thin actin network underlying the plasma membrane in which myosin-driven stresses generate contractile tension. Tension gradients result in local contractions and drive cell deformations. Previous cortical tension regulation studies have focused on myosin motors. Here, we show that cortical actin network architecture is equally important. First, we observe that actin cortex thickness and tension are inversely correlated during cell-cycle progression. We then show that the actin filament length regulators CFL1, CAPZB and DIAPH1 regulate mitotic cortex thickness and find that both increasing and decreasing thickness decreases tension in mitosis. This suggests that the mitotic cortex is poised close to a tension maximum. Finally, using a computational model, we identify a physical mechanism by which maximum tension is achieved at intermediate actin filament lengths. Our results indicate that actin network architecture, alongside myosin activity, is key to cell surface tension regulation.

The mid-Cretaceous vertebrate assemblage from south-eastern Morocco is one of the most diversified continental vertebrate assemblages of this time worldwide. The bony fish component (coelacanths, lungfishes and ray-finned fishes) is represented by relatively complete specimens and, mostly, by fragmentary elements scattered along 250 kilometres of outcrops. Here we revisit the bony fish assemblage by studying both isolated remains collected during several fieldtrips and more complete material kept in public collections. The assemblage comprises several lungfish taxa, with the first mention of the occurrence of Arganodus tiguidiensis, and possibly two mawsoniid coelacanths. A large bichir cf. Bawitius, is recorded and corresponds to cranial elements initially referred to 'Stromerichthys' from coeval deposits in Egypt. The ginglymodians were diversified with a large 'Lepidotes' plus two obaichthyids and a gar. We confirm here that this gar belongs to a genus distinctive from Recent gars, contrary to what was suggested recently. Teleosteans comprise a poorly known ichthyodectiform, a notopterid, a probable osteoglossomorph and a large tselfatiiform, whose cranial anatomy is detailed. The body size and trophic level for each taxon are estimated on the basis of comparison with extant closely related taxa. We plotted the average body size versus average trophic level for the Kem Kem assemblage, together with extant marine and freshwater assemblages. The Kem Kem assemblage is characterized by taxa of proportionally large body size, and by a higher average trophic level than the trophic level of the extant compared freshwater ecosystems, but lower than for the extant marine ecosystems. These results should be regarded with caution because they rest on a reconstructed assemblage known mostly by fragmentary remains. They reinforce, however, the ecological oddities already noticed for this mid-Cretaceous vertebrate ecosystem in North Africa.

Several lineages of endoparasitoid wasps, which develop inside the body of other insects, have domesticated viruses, used as delivery tools of essential virulence factors for the successful development of their progeny. Virus domestications are major evolutionary transitions in highly diverse parasitoid wasps. Much progress has recently been made to characterize the nature of these ancestrally captured endogenous viruses that have evolved within the wasp genomes. Virus domestication from different viral families occurred at least three times in parasitoid wasps. This evolutionary convergence led to different strategies. Polydnaviruses (PDVs) are viral gene transfer agents and virus-like particles of the wasp Venturia canescens deliver proteins. Here, we take the standpoint of parasitoid wasps to review current knowledge on virus domestications by different parasitoid lineages. Then, based on genomic data from parasitoid wasps, PDVs and exogenous viruses, we discuss the different evolutionary steps required to transform viruses into vehicles for the delivery of the virulence molecules that we observe today. Finally, we discuss how endoparasitoid wasps manipulate host physiology and ensure parasitism success, to highlight the possible advantages of viral domestication as compared with other virulence strategies.

Transcriptional elongation is a generic function, but is also regulated to allow rapid transcription responses. Following relatively long initiation and promoter clearance, RNA polymerase II can pause and then rapidly elongate following recruitment of positive elongation factors. Multiple elongation complexes exist, but the role of specific components in adult Drosophila is underexplored.

Tissue morphogenesis requires the collective, coordinated motion and deformation of a large number of cells. Vertex model simulations for tissue mechanics have been developed to bridge the scales between force generation at the cellular level and tissue deformation and flows. We review here various formulations of vertex models that have been proposed for describing tissues in two and three dimensions. We discuss a generic formulation using a virtual work differential, and we review applications of vertex models to biological morphogenetic processes. We also highlight recent efforts to obtain continuum theories of tissue mechanics, which are effective, coarse-grained descriptions of vertex models.This article is part of the themed issue 'Systems morphodynamics: understanding the development of tissue hardware'.

Most mammals, birds, and reptiles are readily recognized by their hairs, feathers, and scales, respectively. However, the lack of fossil intermediate forms between scales and hairs and substantial differences in their morphogenesis and protein composition have fueled the controversy pertaining to their potential common ancestry for decades. Central to this debate is the apparent lack of an "anatomical placode" (that is, a local epidermal thickening characteristic of feathers' and hairs' early morphogenesis) in reptile scale development. Hence, scenarios have been proposed for the independent development of the anatomical placode in birds and mammals and parallel co-option of similar signaling pathways for their morphogenesis. Using histological and molecular techniques on developmental series of crocodiles and snakes, as well as of unique wild-type and EDA (ectodysplasin A)-deficient scaleless mutant lizards, we show for the first time that reptiles, including crocodiles and squamates, develop all the characteristics of an anatomical placode: columnar cells with reduced proliferation rate, as well as canonical spatial expression of placode and underlying dermal molecular markers. These results reveal a new evolutionary scenario where hairs, feathers, and scales of extant species are homologous structures inherited, with modification, from their shared reptilian ancestor's skin appendages already characterized by an anatomical placode and associated signaling molecules.

In vertebrates, skin colour patterns emerge from nonlinear dynamical microscopic systems of cell interactions. Here we show that in ocellated lizards a quasi-hexagonal lattice of skin scales, rather than individual chromatophore cells, establishes a green and black labyrinthine pattern of skin colour. We analysed time series of lizard scale colour dynamics over four years of their development and demonstrate that this pattern is produced by a cellular automaton (a grid of elements whose states are iterated according to a set of rules based on the states of neighbouring elements) that dynamically computes the colour states of individual mesoscopic skin scales to produce the corresponding macroscopic colour pattern. Using numerical simulations and mathematical derivation, we identify how a discrete von Neumann cellular automaton emerges from a continuous Turing reaction-diffusion system. Skin thickness variation generated by three-dimensional morphogenesis of skin scales causes the underlying reaction-diffusion dynamics to separate into microscopic and mesoscopic spatial scales, the latter generating a cellular automaton. Our study indicates that cellular automata are not merely abstract computational systems, but can directly correspond to processes generated by biological evolution.

Understanding how speciation relates to ecological divergence has long fascinated biologists. It is assumed that ecological divergence is essential to sympatric speciation, as a mechanism to avoid competition and eventually lead to reproductive isolation, while divergence in allopatry is not necessarily associated with niche differentiation. The impact of the spatial context of divergence on the evolutionary rates of abiotic dimensions of the ecological niche has rarely been explored for an entire clade. Here, we compare the magnitude of climatic niche shifts between sympatric versus allopatric divergence of lineages in butterflies. By combining next-generation sequencing, parametric biogeography and ecological niche analyses applied to a genus-wide phylogeny of Palaearctic butterflies, we compare evolutionary rates along eight climatic dimensions across sister lineages that diverged in large-scale sympatry versus allopatry. In order to examine the possible effects of the spatial scale at which sympatry is defined, we considered three sets of biogeographic assignments, ranging from narrow to broad definition. Our findings suggest higher rates of niche evolution along all climatic dimensions for sister lineages that diverge in sympatry, when using a narrow delineation of biogeographic areas. This result contrasts with significantly lower rates of climatic niche evolution found in cases of allopatric speciation, despite the biogeographic regions defined here being characterized by significantly different climates. Higher rates in allopatry are retrieved when biogeographic areas are too widely defined-in such a case allopatric events may be recorded as sympatric. Our results reveal the macro-evolutionary significance of abiotic niche differentiation involved in speciation processes within biogeographic regions, and illustrate the importance of the spatial scale chosen to define areas when applying parametric biogeographic analyses.