Development and Evolution of the Vertebrate Hypothalamus: Evidences in Chondrichthyans

The hypothalamus is a conserved integrative center with a complex organization result of a complex patterning processes. Here we make use of a evo-devo approach and the theoretical framework of the prosomeric model to understand the organization of the vertebrate hypothalamus. We studied the gene expression patterns of ScFoxg1a, ScDlx2/5, ScOtp, ScShh, ScNkx2.1, ScTbr1, ScNeurog2, ScLhx5, ScLhx9, ScDlx2/5, ScNkx2.8, ScEmx2, ScLmx1b, ScPitx2, ScPitx3a, ScNeurog2, ScFoxa1 and ScFoxa2 besides immunoreactivity to Pax6, PCNA and other immunomarkers in the embryonic hypothalamus and neighbour prosencephalic territories of a cartilaginous fish, the catshark, Scyliorhinus canicula. Our comparative analysis reveals the existence of conserved traits but also suggests an alternative organization to that proposed by the prosomeric model for the hypothalamus and even for the anterior prosencephalon of vertebrates

Expression of radial glial markers (GFAP, BLBP and GS) during telencephalic development in the catshark (Scyliorhinus canicula)

Radial glial cells (RGCs) are the first cell populations of glial nature to appear during brain ontogeny. They act as primary progenitor (stem) cells as well as a scaffold for neuronal migration. The proliferative capacity of these cells, both in development and in adulthood, has been subject of interest during past decades. In contrast with mammals where RGCs are restricted to specific ventricular areas in the adult brain, RGCs are the predominant glial element in fishes. However, developmental studies on the RGCs of cartilaginous fishes are scant. We have studied the expression patterns of RGCs markers including glial fibrillary acidic protein (GFAP), brain lipid binding protein (BLBP), and glutamine synthase (GS) in the telencephalic hemispheres of catshark (Scyliorhinus canicula) from early embryos to post-hatch juveniles. GFAP, BLBP and GS are first detected, respectively, in early, intermediate and late embryos. Expression of these glial markers was observed in cells with radial glia morphology lining the telencephalic ventricles, as well as in their radial processes and endfeet at the pial surface and their expression continue in ependymal cells (or tanycytes) in early juveniles. In addition, BLBP- and GS-immunoreactive cells morphologically resembling oligodendrocytes were observed. In late embryos, most of the GFAP- and BLBP-positive RGCs also coexpress GS and show proliferative activity. Our results indicate the existence of different proliferating subpopulations of RGCs in the embryonic ventricular zone of catshark. Further investigations are needed to determine whether these proliferative RGCs could act as neurogenic and/or gliogenic precursors.This work was supported by the Spanish Ministerio de Economía y Competitividad-FEDER (BFU2014-5863-1P); Xunta de Galicia-FEDER, Grant number: Rede Galega INBIOEST ED341D R2016/032S

Developmental genoarchitectonics as a key tool to interpret the mature anatomy of the chondrichthyan hypothalamus according to the prosomeric model

The hypothalamus is a key vertebrate brain region involved in survival and physiological functions. Understanding hypothalamic organization and evolution is important to deciphering many aspects of vertebrate biology. Recent comparative studies based on gene expression patterns have proposed the existence of hypothalamic histogenetic domains (paraventricular, TPa/PPa; subparaventricular, TSPa/PSPa; tuberal, Tu/RTu; perimamillary, PM/PRM; and mamillary, MM/RM), revealing conserved evolutionary trends. To shed light on the functional relevance of these histogenetic domains, this work aims to interpret the location of developed cell groups according to the prosomeric model in the hypothalamus of the catshark Scyliorhinus canicula, a representative of Chondrichthyans (the sister group of Osteichthyes, at the base of the gnathostome lineage). To this end, we review in detail the expression patterns of ScOtp, ScDlx2, and ScPitx2, as well as Pax6-immunoreactivity in embryos at stage 32, when the morphology of the adult catshark hypothalamus is already organized. We also propose homologies with mammals when possible. This study provides a comprehensive tool to better understand previous and novel data on hypothalamic development and evolutionThis work was supported by Ministerio de Economía, Industria y Competitividad – Agencia Estatal de Investigación (grant No. BFU2017-89861-P) partially financed by the European Social Fund, and by Xunta de Galicia (grant No. ED431C 2021/18)S

Prosomeric organization of the hypothalamus in an elasmobranch, the catshark Scyliorhinus canicula

The hypothalamus has been a central topic in neuroanatomy because of its important physiological functions, but its mature organization remains elusive. Deciphering its embryonic and adult organization is crucial in an evolutionary approach of the organization of the vertebrate forebrain. Here we studied the molecular organization of the hypothalamus and neighboring telencephalic domains in a cartilaginous fish, the catshark, Scyliorhinus canicula, focusing on ScFoxg1a, ScShh, ScNkx2.1, ScDlx2/5, ScOtp, and ScTbr1 expression profiles and on the identification αacetylated-tubulin-immunoreactive (ir), TH-ir, 5-HT-ir, and GFAP-ir structures by means of immunohistochemistry. Analysis of the results within the updated prosomeric model framework support the existence of alar and basal histogenetic compartments in the hypothalamus similar to those described in the mouse, suggesting the ancestrality of these subdivisions in jawed vertebrates. These data provide new insights into hypothalamic organization in cartilaginous fishes and highlight the generality of key features of the prosomeric model in jawed vertebrates.This work was supported by grants from the Spanish Dirección General de Investigación-FEDER (BFU2010- 15816), the Xunta de Galicia (10PXIB200051PR, CN 2012/237), European Community-Research Infrastructure Action under the FP7 “Capacities” Specific Programme (ASSEMBLE 227799), the Région Centre, Région Bretagne (EVOVERT grant number 049755; PEPTISAN project), National Research Agency (grant ANR-09-BLAN-026201), CNRS, Université d’Orléans and Université Pierre et Marie Curie. GNSD would like to thank Spanish SEPE for its funding supportS

Design and implementation of the AMIGA embedded system for data acquisition

International audienceThe Auger Muon Infill Ground Array (AMIGA) is part of the AugerPrime upgrade of the Pierre Auger Observatory. It consists of particle counters buried 2.3 m underground next to the water-Cherenkov stations that form the 23.5 km2 large infilled array. The reduced distance between detectors in this denser area allows the lowering of the energy threshold for primary cosmic ray reconstruction down to about 1017 eV. At the depth of 2.3 m the electromagnetic component of cosmic ray showers is almost entirely absorbed so that the buried scintillators provide an independent and direct measurement of the air showers muon content. This work describes the design and implementation of the AMIGA embedded system, which provides centralized control, data acquisition and environment monitoring to its detectors. The presented system was firstly tested in the engineering array phase ended in 2017, and lately selected as the final design to be installed in all new detectors of the production phase. The system was proven to be robust and reliable and has worked in a stable manner since its first deployment

The energy spectrum of cosmic rays beyond the turn-down around \varvec{10^{17}} eV as measured with the surface detector of the Pierre Auger Observatory

International audienceWe present a measurement of the cosmic-ray spectrum above 100 PeV using the part of the surface detector of the Pierre Auger Observatory that has a spacing of 750 m. An inflection of the spectrum is observed, confirming the presence of the so-called second-knee feature. The spectrum is then combined with that of the 1500 m array to produce a single measurement of the flux, linking this spectral feature with the three additional breaks at the highest energies. The combined spectrum, with an energy scale set calorimetrically via fluorescence telescopes and using a single detector type, results in the most statistically and systematically precise measurement of spectral breaks yet obtained. These measurements are critical for furthering our understanding of the highest energy cosmic rays

Constraining the sources of ultra-high-energy cosmic rays across and above the ankle with the spectrum and composition data measured at the Pierre Auger Observatory

In this work we present the interpretation of the energy spectrum and mass composition data as measured by the Pierre Auger Collaboration above $6 \times 10^{17}$ eV. We use an astrophysical model with two extragalactic source populations to model the hardening of the cosmic-ray flux at around $5\times 10^{18}$ eV (the so-called "ankle" feature) as a transition between these two components. We find our data to be well reproduced if sources above the ankle emit a mixed composition with a hard spectrum and a low rigidity cutoff. The component below the ankle is required to have a very soft spectrum and a mix of protons and intermediate-mass nuclei. The origin of this intermediate-mass component is not well constrained and it could originate from either Galactic or extragalactic sources. To the aim of evaluating our capability to constrain astrophysical models, we discuss the impact on the fit results of the main experimental systematic uncertainties and of the assumptions about quantities affecting the air shower development as well as the propagation and redshift distribution of injected ultra-high-energy cosmic rays (UHECRs)

Constraining the sources of ultra-high-energy cosmic rays across and above the ankle with the spectrum and composition data measured at the Pierre Auger Observatory

In this work we present the interpretation of the energy spectrum and mass composition data as measured by the Pierre Auger Collaboration above $6 \times 10^{17}$ eV. We use an astrophysical model with two extragalactic source populations to model the hardening of the cosmic-ray flux at around $5\times 10^{18}$ eV (the so-called "ankle" feature) as a transition between these two components. We find our data to be well reproduced if sources above the ankle emit a mixed composition with a hard spectrum and a low rigidity cutoff. The component below the ankle is required to have a very soft spectrum and a mix of protons and intermediate-mass nuclei. The origin of this intermediate-mass component is not well constrained and it could originate from either Galactic or extragalactic sources. To the aim of evaluating our capability to constrain astrophysical models, we discuss the impact on the fit results of the main experimental systematic uncertainties and of the assumptions about quantities affecting the air shower development as well as the propagation and redshift distribution of injected ultra-high-energy cosmic rays (UHECRs)

Arrival Directions of Cosmic Rays above 32 EeV from Phase One of the Pierre Auger Observatory

A promising energy range to look for angular correlation between cosmic rays of extragalactic origin and their sources is at the highest energies, above few tens of EeV ($1\:{\rm EeV}\equiv 10^{18}\:$eV). Despite the flux of these particles being extremely low, the area of ${\sim}\:3{,}000 \: \text{km}^2$ covered at the Pierre Auger Observatory, and the 17-year data-taking period of the Phase 1 of its operations, have enabled us to measure the arrival directions of more than 2,600 ultra-high energy cosmic rays above $32\:\text{EeV}$. We publish this data set, the largest available at such energies from an integrated exposure of $122{,}000 \: \text{km}^2\:\text{sr}\:\text{yr}$, and search it for anisotropies over the $3.4\pi$ steradians covered with the Observatory. Evidence for a deviation in excess of isotropy at intermediate angular scale, with ${\sim}\:15^\circ$ Gaussian spread or ${\sim}\:25^\circ$ top-hat radius, is obtained at the $4\:\sigma$ significance level for cosmic-ray energies above ${\sim}\:40\:\text{EeV}$

Arrival Directions of Cosmic Rays above 32 EeV from Phase One of the Pierre Auger Observatory

International audienceA promising energy range to look for angular correlations between cosmic rays of extragalactic origin and their sources is at the highest energies, above a few tens of EeV (1 EeV ≡ 10$^{18}$ eV). Despite the flux of these particles being extremely low, the area of ∼3000 km$^{2}$ covered at the Pierre Auger Observatory, and the 17 yr data-taking period of the Phase1 of its operations, have enabled us to measure the arrival directions of more than 2600 ultra-high-energy cosmic rays above 32 EeV. We publish this data set, the largest available at such energies from an integrated exposure of 122,000 km$^{2}$ sr yr, and search it for anisotropies over the 3.4π steradians covered with the Observatory. Evidence for a deviation in excess of isotropy at intermediate angular scales, with ∼15° Gaussian spread or ∼25° top-hat radius, is obtained at the 4σ significance level for cosmic-ray energies above ∼40 EeV