Publications

Global analyses of gene expression during development reveal specific transcription patterns associated with the emergence of various cell types, tissues, and organs. These heterogeneous patterns are instrumental to ensure the proper formation of the different parts of our body, as shown by the phenotypic effects generated by functional genetic approaches. However, variations at the cellular level can be observed within each structure or organ. In the developing mammalian limbs, expression of Hox genes from the HoxD cluster is differentially controlled in space and time, in cells that will pattern the digits and the forearms. While the Hoxd genes broadly share a common regulatory landscape and large-scale analyses have suggested a homogenous Hox gene transcriptional program, it has not previously been clear whether Hoxd genes are expressed together at the same levels in the same cells.

Schizophrenia is a severely debilitating neurodevelopmental disorder. Establishing a causal link between circuit dysfunction and particular behavioral traits that are relevant to schizophrenia is crucial to shed new light on the mechanisms underlying the pathology. We studied an animal model of the human 22q11 deletion syndrome, the mutation that represents the highest genetic risk of developing schizophrenia. We observed a desynchronization of hippocampal neuronal assemblies that resulted from parvalbumin interneuron hypoexcitability. Rescuing parvalbumin interneuron excitability with pharmacological or chemogenetic approaches was sufficient to restore wild-type-like CA1 network dynamics and hippocampal-dependent behavior during adulthood. In conclusion, our data provide insights into the network dysfunction underlying schizophrenia and highlight the use of reverse engineering to restore physiological and behavioral phenotypes in an animal model of neurodevelopmental disorder.

Abstract and depictive representations produced by drawing-known from Europe, Africa and Southeast Asia after 40,000 years ago-are a prime indicator of modern cognition and behaviour1. Here we report a cross-hatched pattern drawn with an ochre crayon on a ground silcrete flake recovered from approximately 73,000-year-old Middle Stone Age levels at Blombos Cave, South Africa. Our microscopic and chemical analyses of the pattern confirm that red ochre pigment was intentionally applied to the flake with an ochre crayon. The object comes from a level associated with stone tools of the Still Bay techno-complex that has previously yielded shell beads, cross-hatched engravings on ochre pieces and a variety of innovative technologies2-5. This notable discovery pre-dates the earliest previously known abstract and figurative drawings by at least 30,000 years. This drawing demonstrates the ability of early Homo sapiens in southern Africa to produce graphic designs on various media using different techniques.

During corticogenesis, ventricular zone progenitors sequentially generate distinct subtypes of neurons, accounting for the diversity of neocortical cells and the circuits they form. While activity-dependent processes are critical for the differentiation and circuit assembly of postmitotic neurons, how bioelectrical processes affect nonexcitable cells, such as progenitors, remains largely unknown. Here, we reveal that, in the developing mouse neocortex, ventricular zone progenitors become more hyperpolarized as they generate successive subtypes of neurons. Experimental in vivo hyperpolarization shifted the transcriptional programs and division modes of these progenitors to a later developmental status, with precocious generation of intermediate progenitors and a forward shift in the laminar, molecular, morphological, and circuit features of their neuronal progeny. These effects occurred through inhibition of the Wnt-beta-catenin signaling pathway by hyperpolarization. Thus, during corticogenesis, bioelectric membrane properties are permissive for specific molecular pathways to coordinate the temporal progression of progenitor developmental programs and thus neocortical neuron diversity.

Tissue shape is often established early in development and needs to be scaled isotropically during growth. However, the cellular contributors and ways by which cells interact tissue-wide to enable coordinated isotropic tissue scaling are not yet understood. Here, we follow cell and tissue shape changes in the zebrafish retinal neuroepithelium, which forms a cup with a smooth surface early in development and maintains this architecture as it grows. By combining 3D analysis and theory, we show how a global increase in cell height can maintain tissue shape during growth. Timely cell height increase occurs concurrently with a non-cell-autonomous actin redistribution. Blocking actin redistribution and cell height increase perturbs isotropic scaling and leads to disturbed, folded tissue shape. Taken together, our data show how global changes in cell shape enable isotropic growth of the developing retinal neuroepithelium, a concept that could also apply to other systems.

Boundaries (insulators) in the bithorax complex (BX-C) delimit autonomous regulatory domains that orchestrate the parasegment (PS)-specific expression of the BX-C homeotic genes. The boundary separates the and regulatory domains, which control Abd-B expression in PS11 and PS12, respectively. This boundary is composed of multiple functionally redundant elements and has two key functions: it blocks crosstalk between and and facilitates boundary bypass. Here, we show that two BEN domain protein complexes, Insensitive and Elba, bind to multiple sequences located in the nuclease hypersensitive regions. Two of these sequences are recognized by both Insv and Elba and correspond to a CCAATTGG palindrome. Elba also binds to a related CCAATAAG sequence, while Insv does not. However, the third Insv recognition sequences is ~100 bp in length and contains the CCAATAAG sequence at one end. Both Insv and Elba are assembled into large complexes (~420 kD and ~265-290 kD, respectively) in nuclear extracts. Using a sensitized genetic background we show that the Insv protein is required for boundary function, and that PS11 identity is not properly established in mutants. This is the first demonstration that a BEN domain protein is important for the functioning of an endogenous fly boundary.

Two marine members of the genus Vexillifera Schaeffer, 1926 (Amoebozoa, Dactylopodida) are described. Vexillifera abyssalis n. sp. originates from an abyssal sample of the Western Atlantic 4.5 km deep, which is the first unambiguous record of a deep-sea Vexillifera. The second species, V. kereti n. sp. was isolated from the soft bottom sediments of the White Sea (depth 106 m). An analysis of available data on the genus Vexillifera shows that it comprises many different species, yet they are very unevenly studied. The majority of species have only been described using light microscopy, and their phylogenetic relationships with other amoebae are unclear. However, available small-subunit (SSU) rRNA gene sequences of Vexillifera spp. form a robust, yet very heterogeneous clade in the phylogenetic tree. These species demonstrate a wide range of morphological and ultrastructural characters and originate from diverse habitats, suggesting that Vexillifera may need to be subdivided into several genera in the future. In addition to the described species, we sequenced the COI gene of original CCAP strains of Vexillifera bacillipedes, V. minutissima and Pseudoparamoeba pagei, thereby performing a phylogenetic reconstruction of the Dactylopodida based on a decent taxonomic sampling.

Based on a combination of morphological and molecular data, we describe five new species and two new genera of xenophyophores from the Clarion–Clipperton Zone (abyssal eastern Pacific), an area with commercially valuable seafloor deposits of polymetallic nodules. Bizarria bryiformis gen. et sp. nov. displays unusual features, notably an organic-walled test, largely devoid of agglutinated particles, comprising interconnected branches growing upwards from the nodule substrate; the bases of the branches contain dark masses of waste material (stercomare) and pale strands of cytoplasm (granellare), the whitish, tuft-like extremities contain sediment particles. Tendalia reteformis gen. et sp. nov. forms a delicate network of agglutinated tubes. Shinkaiya contorta sp. nov. is characterized by a contorted, partly reticulated plate-like test while the simpler plate-like test of Galatheammina interstincta sp. nov. combines characters typical of Galatheammina and Psammina. In Semipsammina mattaeformis sp. nov., a thin, delicate test with one or more tubular extensions forms a flat canopy over the mat-like stercomare encrusting the nodule substrate. Tendalia reteformis and S. contorta are free-living; the other species are sessile on nodules. Together, they illustrate the considerable morphological diversity of xenophyophores in a region where they dominate the megafauna, and highlight some major taxonomic challenges posed by these giant monothalamous foraminifera.

Ciliates are powerful indicators for monitoring the impact of aquaculture and other industrial activities in the marine environment. Here we tested the efficiency of four different genetic markers (V4 and V9 regions of the SSU rRNA gene, D1 and D2 regions of the LSU rRNA gene, obtained from environmental (e)DNA and environmental (e)RNA) of benthic ciliate communities for environmental monitoring. We obtained these genetic metabarcodes from sediment samples collected along a transect extending from below salmon cages towards the open sea. These data were compared to benchmark data from traditional macrofauna surveys of the same samples. In beta-diversity analyses of ciliate community structures, the V4 and V9 markers had a higher resolution power for sampling sites with different degrees of organic enrichment compared to the D1 and D2 markers. The eDNA and eRNA V4 markers had a higher discriminatory power than the V9 markers. However, results obtained with the eDNA V9 marker corroborated better with the traditional macrofauna monitoring. This allows for a more direct comparison of ciliate metabarcoding with the traditional monitoring. We conclude that the ciliate eDNA V9 marker is the best choice for implementation in routine monitoring programs in marine aquaculture. This article is protected by copyright. All rights reserved.

European genetic gradients of modern humans were initially interpreted as a consequence of the demic diffusion of expanding Neolithic farmers. However, recent studies showed that these gradients may also be influenced by other evolutionary processes such as population admixture or range contractions. Genetic gradients were observed in the Americas, although their specific evolutionary causes were not investigated. Here we extended the approach used to study genetic gradients in Europe to analyze the influence of diverse evolutionary scenarios on American genetic gradients. Using extensive computer simulations, we evaluated the impact of (i) admixture between expansion waves of modern humans, (ii) the presence of ice-sheets during the last glacial maximum (LGM) and (iii) long-distance dispersal (LDD) events, on the genetic gradients (detected by principal component analysis) of the entire continent, North America and South America. The specific simulation of North and South America showed that genetic gradients are usually orthogonal to the direction of range expansions-either expansions from Bering or posterior re-expansions to recolonize northern regions after ice sheets melting-and we suggest that they result from allele surfing processes. Conversely, our results on the entire continent show a northwest-southeast gradient obtained with any scenario, which we interpreted as a consequence of isolation by distance along the long length of the continent. These findings suggest that distinct genetic gradients can be detected at different regions of the Americas and that subcontinent regions present gradients more sensible to evolutionary and environmental factors (such as LDD and the LGM) than the whole continent.