Elucidating the key mechanisms underlying rare genetic disorders is particularly challenging, as their phenotypes typically manifest from the earliest stages of development. While ‘rare’ suggests these diseases are marginal problems, collectively millions of individuals are affected, often with diagnostic uncertainties and no therapeutic options. Yet the rarity of individual diseases implies that classical clinical studies are not possible and costly drug development fails to meet a sufficiently large clientele. Therefore, it is critical to develop cost effective predictive disease models that could facilitate the translation of molecular mechanistic insights. Likewise, we need to develop a more comprehensive view on certain disorders that appear phenotypically similar. Here we hypothesize that two major rare disease families, RASopathies and ciliopathies, which have several phenotypic similarities also share a common mechanistic denominator: defective cilia function. Primary cilia are the ‘antennae’ of the stem- and progenitor cells that host critical developmental pathways. Based on our most recent data, we argue that the RAS pathway fundamentally affects ciliogenesis in a differentiating system. Notably KRAS may protect ciliation and thus stemness during asymmetric cell divisions, thus fundamentally shaping cell differentiation hierarchies. As small imbalances in cellular hierarchies accumulate throughout development, we end up with exponentially aggravated defects in multiple organ systems as typically seen in these disorders. We discuss how simple cellular differentiation models in combination with zebrafish disease models may have the potential to drive not only our understanding of the underpinning molecular and cellular process but also enable drug screening. We propose that primary cilia are important to understand several developmental diseases and also tissue homeostasis in the adult.
The origin of the vertebrate jaw is one of the most long-standing and enigmatic topics in vertebrate evolution. To address this fundamental problem, lamprey larvae have long been the primary source of information on the cranial system of jawless vertebrates. However, their cranial anatomy remains contentious, largely because previous anatomical studies have relied primarily on conventional methodologies, leaving room for subjective identification. Here, we focused on cranial muscles whose morphology and innervation have been particularly controversial, performing high-resolution and objective imaging of the muscles and trigeminal nerve branches in three dimensions using various advanced techniques, including micro-computed tomography and light-sheet microscopy. Our detailed observations revealed several key characters that have previously been overlooked. First, an undescribed upper lip muscle is innervated by a sub-branch of the second major branch of the trigeminal nerve, which had long been thought to be purely sensory. Second, most lower lip muscles exhibit dual innervation by the second and third major branches of the trigeminal nerve. Last, the topographical arrangement of the lower lip muscle was elucidated in detail for the first time, suggesting that this muscle gives rise to the musculature of adult lingual apparatus through metamorphosis. Our three-dimensional data revises previous views on the cranial morphology of lamprey larvae and provides a solid foundation for comparative morphological and developmental studies across extinct and extant vertebrates. In addition, the cutting-edge imaging methods employed here could be applied to metamorphic and adult lampreys, offering a promising approach for elucidating the morphogenesis of the adult head. Taken together, this study opens new avenues for evolutionary developmental and paleontological research on the early evolution of vertebrate heads.
Cartilaginous fishes (chondrichthyans) from the Devonian period (419–359 million years, Ma) are primarily known from fossilized isolated dermal elements such as teeth, scales, and fin spines. Although previous studies have described the morphology and the histology of these elements, their developmental patterns remain poorly understood. In this study, we propose to explore developmental patterns of early chondrichthyan fin spines by integrating paleohistological cuts, micro-CT scan, SEM and microscopy analyses. We present the first description of the developmental patterns for the fin spines of the Middle Devonian chondrichthyan Wellerodus priscus, from the Cairo Quarry Lagerstätte in New York State, USA. Based on the ornamentation pattern and paleohistological (thin sections and micro-CT scan) characteristics, we identify a longitudinal (length wise) growth and a transverse (width wise) growth, each associated with specific zones of tissue production in the pectoral and dorsal fin spines of W. priscus. Spine developmental patterns observed in Wellerodus are compared among Paleozoic total-group chondrichthyans composed by the stem-chondrichthyans “acanthodians” and the crown group. Our framework offers a new line of evidence for understanding the evolution of fin spine development by showing that Wellerodus priscus fin spines grow in length and in width. It enhances our comprehension of developmental similarities between early chondrichthyans and more derived Carboniferous, Permian, and even extant chondrichthyans. The histo-morphological criteria used to describe this developmental pattern provide characters potentially suitable for phylogenetic analyses.
Bristly millipedes face many challenges regarding fossilisation (i.e., soft body, hidden living environments) and are clearly under-represented in the literature. Surprisingly, they are quite common in amber, offering an exceptional window to investigate their evolutionary history of the past 100 million years. Hundreds of inclusions in amber that cover the almost complete ontogenetic sequence of both Polyxenidae and Synxenidae have been investigated, and for each specimen distances between ten landmarks are measured. In contradiction to previous expectations, representatives of both Polyxenidae and Synxenidae have significantly changed through time, going from “dwarfs” during the Cretaceous ( 100 Ma) to “giants” during the Eocene ( 35 Ma); extant representatives are found in-between. This first attempt in investigating morphological changes in bristly millipedes may suggest the potential influence of the environment on the evolutionary trajectories within this group. The Cretaceous was a time of warmer climates, with tropical rainforests on the Burma Terrane, while the Eocene and modern-day representatives are from equable and temperate regions. Potentially, the environmental conditions on the Burma Terrane pressured bristly millipedes to reach “dwarf” sizes. The observed signals may be an indication of the Temperature-Size Rule, favouring quick development while slow growth in warmer ecosystems.
Understanding the concept of deep time is essential for comprehending evolutionary processes, yet research indicates that learners often struggle with grasping vast geological time scales. This study examines the understanding of deep time of first-year university students across 26 European countries and examines its relationship with knowledge about evolution and acceptance of evolution. We assessed students’ estimations of key historical events, including the origin of life, the existence of dinosaurs, and the emergence of humans. The results indicate that while most students correctly sequence these events, many hold substantial misconceptions regarding their absolute time frames and points in time. Statistical analyses reveal a weak correlation between the understanding of deep time and knowledge of evolution, while no significant correlation was found between the understanding of deep time and acceptance of evolution. These findings suggest that deep time is a distinct conceptual domain that requires targeted educational approaches. Additionally, notable differences between country samples highlight the potential influence of curriculum design, cultural factors, and prior education. Given the fundamental role of deep time in understanding evolutionary change, climate change, and biodiversity loss, there is a clear need for effective educational strategies and innovative teaching tools to enhance students’ comprehension.
