Abstract 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.
Ornithocheirus wiedenrothi, from the Hauterivian (Early Cretaceous of Germany), is a taxon represented by three-dimensional remains of the lower jaw and wing elements. Its phylogenetic affinities have for long been elusive, though several works had already pointed out that it probably did not belong within the wastebasket genus Ornithocheirus. In the present contribution, we redescribe this species, assigning it to the new genus Targaryendraco and offering updated morphological comparisons. Subsequently, we present a phylogenetic analysis in which we recover a clade formed by Targaryendraco, Aussiedraco, Barbosania, Aetodactylus, Camposipterus and Cimoliopterus. This newly recognised clade is interesting in being quite cosmopolitan and spanning from the Hauterivian to the Cenomanian, like its sister-group, the Anhangueria. The recognition of this clade helps fill the temporal gap between the Anhangueria and Cimoliopterus, and also demonstrates that the diversity of Cretaceous toothed pterosaurs was higher than previously thought.
A 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.
Summary The study of the origin and development of cerebellar tumours has been hampered by the complexity and heterogeneity of cerebellar cells that change over the course of development. We used single-cell transcriptomics to study >60,000 cells from the developing murine cerebellum, and show that different molecular subgroups of childhood cerebellar tumors mirror the transcription of cells from distinct, temporally restricted cerebellar lineages. Sonic Hedgehog medulloblastoma transcriptionally mirrors the granule cell hierarchy as expected, whereas Group 3 medulloblastoma resemble Nestin +ve stem cells, Group 4 medulloblastomas resemble unipolar brush cells, and PFA/PFB ependymoma and cerebellar pilocytic astrocytoma resemble the prenatal gliogenic progenitor cells. Furthermore, single-cell transcriptomics of human childhood cerebellar tumors demonstrates that many bulk tumors contain a mixed population of cells with divergent differentiation. Our data highlight cerebellar tumors as a disorder of early brain development, and provide a proximate explanation for the peak incidence of cerebellar tumors in early childhood.
microRNAs (miRNAs) have wide-ranging effects on large-scale gene regulation. As such, they play a vital role in dictating normal development, and their aberrant expression has been implicated in cancer. There has been a large body of research on the role of miRNAs in medulloblastoma, the most common malignant brain tumor of childhood. The identification of the 4 molecular subgroups with distinct biological, genetic, and transcriptional features has revolutionized the field of medulloblastoma research over the past 5 years. Despite this, the growing body of research on miRNAs in medulloblastoma has largely focused on the clinical entity of a single disease rather than the molecular subgroups. This review begins by highlighting the role of miRNAs in development and progresses to explore their myriad of implications in cancer. Medulloblastoma is characterized by increased proliferation, inhibition of apoptosis, and maintenance of stemness programs—features that are inadvertently regulated by altered expression patterns in miRNAs. This review aims to contextualize the large body of work on miRNAs within the framework of medulloblastoma subgroups. The goal of this review is to stimulate new areas of research, including potential therapeutics, within a rapidly growing field.
After more than a decade of genomic studies in medulloblastoma, the time has come to capitalize on the knowledge gained and use it to directly improve patient care. Although metastatic and relapsed disease remain poorly understood, much has changed in how we define medulloblastoma, and it has become evident that with conventional therapies, specific groups of patients are currently under- or overtreated. In this review, we summarize the latest insights into medulloblastoma biology, focusing on how genomics is affecting patient stratification, informing preclinical studies of targeted therapies, and shaping the new generation of clinical trials.
We isolated cells from various points in murine embryonic and early post-ntal cerebellar development (E10 to P14) and undertook single cell RNA sequencing to identify >30 transcriptionally distinct cell populations. Reconstruction of developmental lineages in the developing cerebellum through pseudotemporal analysis demonstrate that a progenitor cell population from the upper rhombic lip gives rise to both the external granule cell layer (EGL) and the previously under-studied unipolar brush cells (UBC). Unipolar brush cells are a glutamatergic interneuron most prevalent in the inferior and lateral cerebellum. Transcriptional matching of bulk human tumor RNA-seq data from human patients demonstrates subgroup specific transcriptional resemblances. As expected, Shh MBs resemble the developing EGL. Fascinatingly, only Shh tumors that transcriptionally mirror earlier, but not later EGL developmental time points were found to be metastatic in human patients. Group 3 tumors have a resemblance to early Nestin +ve stem cells across the entire subgroup, with additional similarities to the EGL, UBC, and GABAergic interneurons. Unexpectedly, Group 4 tumors were vastly most similar to UBCs, and on further analysis to a single known subset of UBCs (Calb2+ve UBCs). Single cell RNA-seq from human medulloblastomas (Shh, Group 3, and Group 4 MB) largely confirms the transcriptional similarities to murine cerebellar developmental lineages observed in the bulk RNA-seq data, but also demonstrates that most medulloblastomas have multiple distinct tumor cell clusters. Distinct single cell expression clusters from an individual MB demonstrate that there is a developmental lineage or hierarchy of cells with most tumors, that this hierarchy is likely hardwired from normal development, and that bulk tumor data in fact reflects a heterogeneous cell population. These data pinpoint possible cells of origin for medulloblastoma subgroups, illustrate a further layer of MB heterogeneity, and allow a comparison of normal and MB transcriptomes to further understand MB biology.
