A taxonomic and phylogenetic review of the anhanguerid pterosaur group Coloborhynchinae and the new clade Tropeognathinae

Anhanguerids are a particular group of pterodactyloid pterosaurs, characterized mainly by their rostral sagittal crests, well laterally expanded jaw tips and enlarged anterior teeth. Due to the fragmentary nature of most known specimens, including holotypes, the taxonomy of the group has proved particularly difficult and controversial. Coloborhynchinae is a recently proposed clade within the Anhangueridae, and was defined as the most inclusive clade containing Coloborhynchus clavirostris but not Anhanguera or Ludodactylus. Coloborhynchinae was originally thought to include Coloborhynchus, Uktenadactylus, and Siroccopteryx. Here we present a reassessment of the taxonomy and phylogeny of all proposed members of the Coloborhynchinae and Coloborhynchus complex, with new anatomical comparisons and a novel phylogenetic analysis. Several features allow us to establish that coloborhynchines were much more diverse than previously thought, englobing four genera and seven species: Aerodraco sedgwickii gen. et comb. nov., Coloborhynchus clavirostris, Nicorhynchus capito gen. et comb. nov., Nicorhynchus fluviferox gen. et comb. nov., Uktenadactylus rodriguesae sp. nov., and Uktenadactylus wadleighi. Nicorhynchus and Uktenadactylus are considered sister taxa, being distinct on the basis of several rostral characters. Although with a homoplastic flat rostrum surface, Siroccopteryx was recovered out of the Coloborhynchinae, as sister taxon of Tropeognathus, due to similarities on the palatal ridge (which is broad and deep, and starting at the same level) and the relatively stout teeth compared to other anhanguerids. Tropeognathus and Siroccopteryx are further related to the Australian taxa Ferrodraco and Mythunga, which are all grouped in a new clade: the Tropeognathinae. Our analysis suggests that morphological evolution within anhanguerids was quite more complex than previously thought, with coloborhynchines representing the oldest recorded lineage of Anhangueridae, which achieved a worldwide distribution at least from the Aptian to the Cenomanian

Quantitative assessment of the vertebral pneumaticity in an anhanguerid pterosaur using micro-CT scanning

Research on the postcranial skeletal pneumaticity in pterosaurs is common in the literature, but most studies present only qualitative assessments. When quantitative, they are done on isolated bones. Here, we estimate the Air Space Proportion (ASP) obtained from micro-CT scans of the sequence from the sixth cervical to the fourth dorsal vertebra of an anhanguerine pterosaur to understand how pneumaticity is distributed in these bones. Pneumatisation of the vertebrae varied between 68 and 72% of their total volume. The neural arch showed higher ASP in all vertebrae. Anhanguerine vertebral ASP was generally higher than in sauropod vertebrae but lower than in most extant birds. The ASP observed here is lower than that calculated for the appendicular skeleton of other anhanguerian pterosaurs, indicating the potential existence of variation between axial and appendicular pneumatisation. The results point to a pattern in the distribution of the air space, which shows an increase in the area occupied by the trabecular bone in the craniocaudal direction of the vertebral series and, in each vertebra, an increase of the thickness of the trabeculae in the zygapophyses. This indicates that the distribution of pneumatic diverticula in anhanguerine vertebrae may not be associated with stochastic patterns

Novel information on the cranial anatomy of the tapejarine pterosaur Caiuajara dobruskii

Caiuajara dobruskii is a tapejarid pterosaur from the Cretaceous of the 'Cemitério dos Pterossauros' (pterosaur graveyard) site, a unique pterosaur bonebed which is located at the municipality of Cruzeiro do Oeste (Paraná, Brazil). Preliminary inferences on Caiuajara morphology were founded on a few partial skeletons, with no detail on the skull anatomy. Here we describe a new specimen from the pterosaur graveyard site, which corresponds to the most complete skull of Caiuajara dobruskii known so far. Furthermore, we describe and compare other specimens including the holotype, a paratype, and several other undescribed specimens. The new specimen preserves the posterior portion of the skull, allowing a better comprehension of its morphology and provides an appreciation of the anatomic structures of the basicranium, enabling better interpretation of this region. We also described the lower jaw of Caiuajara, reporting a unique feature of its symphyseal which adds to the diagnosis for the species. A variability in the premaxillary crest is also noted in different specimens of Caiuajara, which might be interpreted as sexual dimorphism or ontogenetic variability. Therefore, those new findings allow a better comprehension of its skull and enables a more precise comparison between the skulls of those extinct flying reptiles

First complete pterosaur from the Afro-Arabian continent : insight into pterodactyloid diversity

Despite being known from every continent, the geological record of pterosaurs, the first group of vertebrates to develop powered flight, is very uneven, with only a few deposits accounting for the vast majority of specimens and almost half of the taxonomic diversity. Among the regions that stand out for the greatest gaps of knowledge regarding these flying reptiles, is the Afro-Arabian continent, which has yielded only a small number of very fragmentary and incomplete materials. Here we fill part of that gap and report on the most complete pterosaur recovered from this continent, more specifically from the Late Cretaceous (~95 mya) Hjoûla Lagerstätte of Lebanon. This deposit is known since the Middle Ages for the exquisitely preserved fishes and invertebrates, but not for tetrapods, which are exceedingly rare. Mimodactylus libanensis gen. et sp. nov. differs from the other Afro-Arabian pterosaur species named to date and is closely related to the Chinese species Haopterus gracilis, forming a new clade of derived toothed pterosaurs. Mimodactylidae clade nov. groups species that are related to Istiodactylidae, jointly designated as Istiodactyliformes (clade nov.). Istiodactyliforms were previously documented only in Early Cretaceous sites from Europe and Asia, with Mimodactylus libanensis the first record in Gondwana

On a new crested pterodactyloid from the Early Cretaceous of the Iberian Peninsula and the radiation of the clade Anhangueria

The pterosaur record from the Iberian Peninsula is mostly scarce and undefined, but in the last few years some new taxa have been described from different Lower Cretaceous sites of Spain. Here we describe a new genus and species of toothed pterodactyloid pterosaur from the Barremian of the Iberian Peninsula, Iberodactylus andreui gen. et sp. nov., that shows a close and rather unexpected relationship with Hamipterus tianshanensis from China. A review of the phylogenetic relationships of the Anhangueria reveals a new family of pterodactyloid pterosaurs, the Hamipteridae fam. nov. being recovered as sister-group of the Anhangueridae. This latter clade can be in turn divided into the new clades Anhanguerinae and Coloborhynchinae. The close relationships of Iberodactylus and Hamipterus shows an interesting palaeobiogeographical correlation between the Chinese and Iberian pterosaur faunas during the Barremian (Lower Cretaceous). The discovery of Iberodactylus strongly suggests that the clade Anhangueria has clear ancestral ties in eastern Laurasia

Palaeohistology and palaeopathology of an Aeolosaurini (Sauropoda: Titanosauria) from Morro do Cambambe (Upper Cretaceous, Brazil)

Altres ajuts: CAISEP (Comisión de Ayudas a la Investigación de la Sociedad Española de Paleontología) project #2018-07153A recent publication of fossil bones of titanosaurs assigned to Aeolosaurini from the Morro do Cambambe site (Mato Grosso state, Brazil, Upper Cretaceous) reported anomalous growth in some of them. Here, we present osteohistological sections of elements to understand not only the microstructure and growth of such bones, but also the nature of those anomalies. The primary bone of all specimens consisted of a variation of the fibrolamellar complex, with the inner cortex being rich in woven bone with dispersed longitudinal canals, while the outer cortex was parallel-fibred with rows of longitudinal canals, interlayered by Lines of Arrested Growth (LAGs). We identified a maximum of two LAGs in the cervical rib and haemal arch, and four in the dorsal rib. The haemal arch shows an External Fundamental System (EFS) in most sections. The advanced remodelling and variation of the fibrolamellar bone in the cortex suggests that all the specimens represent individuals that reached sexual maturity. However, the haemal arch was distinct due to the wide distribution of EFS. The dorsal rib exhibited periosteal and endosteal outgrowth. Such microstructure was assigned to a reactive bone due to an intra-thoracic infection (a pneumonia, probably related to a tuberculosis), which is the first report in a non-avian dinosaur. The microstructure resembles the medullary bone recovered in dinosaurs, which suggests that further studies of medullary bone in thoracic bones should also regard the pathological cases.En una reciente publicación de los huesos fósiles de titanosaurios asignados al clado Aeolosaurini provenientes del yacimiento de Morro do Cambambe (estado de Mato Grosso, Brasil, Cretácico Superior), se reconocieron anormalidades en el crecimiento de algunos de ellos. En el presente trabajo presentamos cortes osteohistológicos de elementos para entender no sólo la microestructura y crecimiento de los mismos, sino también la naturaleza de aquellas anomalías. Entre ellos, seleccionamos una costilla cervical y una costilla dorsal media posterior, así como un arco hemal. El hueso primario de todos los especímenes comprendía una variación del complejo fibrolamelar, siendo la corteza interna rica en tejido reticular óseo con canales longitudinales dispersos, mientras que la corteza externa tenía fibras paralelas con hileras de canales longitudinales, intercaladas por líneas de crecimiento detenido. Identificamos un máximo de dos líneas de crecimiento detenido tanto en la costilla cervical como en el arco hemal, y cuatro en la costilla dorsal. El arco hemal muestra un Sistema Externo Fundamental en la mayoría de las secciones. La remodelación avanzada y la variación del hueso fibrolamelar en la corteza, se sugiere que todas los especímenes alcanzaron la madurez sexual. Sin embargo, el arco hemal fue distinto debido a la amplia distribución de Sistema Externo Fundamental. Con base en la microestructura, identificamos un semaforonte subadulto, y probablemente a un adulto. La costilla dorsal mostró una excrecencia perióstica y endosteal. Dicha microestructura se ha identificado con un hueso reactivo a una infección intratorácica (una neumonía, probablemente relacionada con una tuberculosis), que es el primer informe de un dinosaurio no aviano. La microestructura se asemeja al hueso medular recuperado en los dinosaurios, lo que sugiere que los estudios posteriores del hueso medular en los huesos torácicos también deberían considerar los casos patológicos

A new toothless pterosaur (Pterodactyloidea) from Southern Brazil with insights into the paleoecology of a Cretaceous desert

The first pterosaur bone bed from Brazil was reported in 2014 at the outskirts of the town Cruzeiro do Oeste, Paraná State, in the Southern region of the country. Here named 'cemitério dos pterossauros' site, these outcrops were referred to the Goio-Erê Formation (Turonian-Campanian) of the Caiuá Group (Bauru Basin) and revealed the presence of hundreds of isolated or partially articulated elements of the tapejarine pterosaur Caiuajara and fewer amounts of a theropod dinosaur. Here we present a new tapejaromorph flying reptile from this site, Keresdrakon vilsoni gen. et sp. nov., which shows a unique blunt ridge on the dorsal surface of the posterior end of the dentary. Morphological and osteohistological features indicate that all recovered individuals represent late juveniles or sub-adults. This site shows the first direct evidence of sympatry in Pterosauria. The two distinct flying reptiles coexisted with a theropod dinosaur, providing a rare glimpse of a paleobiological community from a Cretaceous desert

CXCL12-mediated murine neural progenitor cell movement Requires PI3Kß activation

The migratory route of neural progenitor/precursor cells (NPC) has a central role in central nervous system development. Although the role of the chemokine CXCL12 in NPC migration has been described, the intracellular signaling cascade involved remains largely unclear. Here we studied the molecular mechanisms that promote murine NPC migration in response to CXCL12, in vitro and ex vivo. Migration was highly dependent on signaling by the CXCL12 receptor, CXCR4. Although the JAK/STAT pathway was activated following CXCL12 stimulation of NPC, JAK activity was not necessary for NPC migration in vitro. Whereas CXCL12 activated the PI3K catalytic subunits p110α and p110β in NPC, only p110β participated in CXCL12-mediated NPC migration. Ex vivo experiments using organotypic slice cultures showed that p110β blockade impaired NPC exit from the medial ganglionic eminence. In vivo experiments using in utero electroporation nonetheless showed that p110β is dispensable for radial migration of pyramidal neurons. We conclude that PI3K p110β is activated in NPC in response to CXCL12, and its activity is necessary for immature interneuron migration to the cerebral cortex.BLH received an FPI predoctoral fellowship (BES-2006-12965) from the Spanish Ministry of Science and Innovation. This work was supported in part by grants from the Spanish Ministry of Science and Innovation (SAF 2011-27370), the RETICS Program (RD08/0075/0010, RD12/0009/0009; RIER), the Madrid regional government (S2010/BMD-2350; RAPHYME), and the European Union (FP7-integrated project Masterswitch 223404).Peer reviewe

Therapeutic targeting of ependymoma as informed by oncogenic enhancer profiling

Genomic sequencing has driven precision-based oncology therapy; however, the genetic drivers of many malignancies remain unknown or non-targetable, so alternative approaches to the identification of therapeutic leads are necessary. Ependymomas are chemotherapy-resistant brain tumours, which, despite genomic sequencing, lack effective molecular targets. Intracranial ependymomas are segregated on the basis of anatomical location (supratentorial region or posterior fossa) and further divided into distinct molecular subgroups that reflect differences in the age of onset, gender predominance and response to therapy1,2,3. The most common and aggressive subgroup, posterior fossa ependymoma group A (PF-EPN-A), occurs in young children and appears to lack recurrent somatic mutations2. Conversely, posterior fossa ependymoma group B (PF-EPN-B) tumours display frequent large-scale copy number gains and losses but have favourable clinical outcomes1,3. More than 70% of supratentorial ependymomas are defined by highly recurrent gene fusions in the NF-κB subunit gene RELA (ST-EPN-RELA), and a smaller number involve fusion of the gene encoding the transcriptional activator YAP1 (ST-EPN-YAP1)1,3,4. Subependymomas, a distinct histologic variant, can also be found within the supratetorial and posterior fossa compartments, and account for the majority of tumours in the molecular subgroups ST-EPN-SE and PF-EPN-SE. Here we describe mapping of active chromatin landscapes in 42 primary ependymomas in two non-overlapping primary ependymoma cohorts, with the goal of identifying essential super-enhancer-associated genes on which tumour cells depend. Enhancer regions revealed putative oncogenes, molecular targets and pathways; inhibition of these targets with small molecule inhibitors or short hairpin RNA diminished the proliferation of patient-derived neurospheres and increased survival in mouse models of ependymomas. Through profiling of transcriptional enhancers, our study provides a framework for target and drug discovery in other cancers that lack known genetic drivers and are therefore difficult to treat.This work was supported by an Alex's Lemonade Stand Young Investigator Award (S.C.M.), The CIHR Banting Fellowship (S.C.M.), The Cancer Prevention Research Institute of Texas (S.C.M., RR170023), Sibylle Assmus Award for Neurooncology (K.W.P.), the DKFZ-MOST (Ministry of Science, Technology & Space, Israel) program in cancer research (H.W.), James S. McDonnell Foundation (J.N.R.) and NIH grants: CA154130 (J.N.R.), R01 CA169117 (J.N.R.), R01 CA171652 (J.N.R.), R01 NS087913 (J.N.R.) and R01 NS089272 (J.N.R.). R.C.G. is supported by NIH grants T32GM00725 and F30CA217065. M.D.T. is supported by The Garron Family Chair in Childhood Cancer Research, and grants from the Pediatric Brain Tumour Foundation, Grand Challenge Award from CureSearch for Children’s Cancer, the National Institutes of Health (R01CA148699, R01CA159859), The Terry Fox Research Institute and Brainchild. M.D.T. is also supported by a Stand Up To Cancer St. Baldrick’s Pediatric Dream Team Translational Research Grant (SU2C-AACR-DT1113)

The transcriptional landscape of Shh medulloblastoma

© The Author(s) 2021. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Sonic hedgehog medulloblastoma encompasses a clinically and molecularly diverse group of cancers of the developing central nervous system. Here, we use unbiased sequencing of the transcriptome across a large cohort of 250 tumors to reveal differences among molecular subtypes of the disease, and demonstrate the previously unappreciated importance of non-coding RNA transcripts. We identify alterations within the cAMP dependent pathway (GNAS, PRKAR1A) which converge on GLI2 activity and show that 18% of tumors have a genetic event that directly targets the abundance and/or stability of MYCN. Furthermore, we discover an extensive network of fusions in focally amplified regions encompassing GLI2, and several loss-of-function fusions in tumor suppressor genes PTCH1, SUFU and NCOR1. Molecular convergence on a subset of genes by nucleotide variants, copy number aberrations, and gene fusions highlight the key roles of specific pathways in the pathogenesis of Sonic hedgehog medulloblastoma and open up opportunities for therapeutic intervention.info:eu-repo/semantics/publishedVersio