Biology subjects

Lowe, C. J.

Publications and source records attributed to Lowe, C. J..

10 recordsLinked to original sources

bioRxiv2026

Development and Validation of the Transcranial Magnetic Stimulation Reporting Assessment Tool(TMS-RAT)

HighlightsO_LIWe introduce the TMS-RAT, a reporting (assessment) tool for TMS studies C_LIO_LIDeveloped within a community-informed, iterative process rating 333 TMS studies C_LIO_LIEmpirically evaluated for usability, inter-rater, and test-retest reliability C_LIO_LIA validated subset enables reliable retrospective assessment of reporting C_LIO_LIThe modular structure enables use across a wide range of TMS study designs C_LI BackgroundA standardised tool for comprehensive reporting can improve transparency, support consistent documentation, and enable comparison across transcranial magnetic stimulation (TMS) studies. The most used reporting checklist lacks clear definitions of full reporting and was not initially evaluated for usability or inter-rater reliability. A scoping review of studies using this checklist shows that its items are reported only 50% of the time, suggesting that method descriptions are often incomplete. MethodsWe developed the TMS Reporting Assessment Tool (TMS-RAT), a comprehensive reporting framework that provides clear definitions and examples for its items, covering a wide range of TMS protocols. We tested the usability and reliability of the TMS-RAT by rating all studies published between 1991 and 2025 using afferent conditioning (n = 333), a protocol encompassing many reporting categories identified during tool development. Seventeen independent raters contributed across three development phases, a validation phase, and a retest phase, with naive raters introduced in each phase. Iterative refinements of the tool were informed by inter-rater reliability, qualitative rater feedback, and consultation with external TMS experts. ResultsWe present two versions of the tool: the 72-item TMS-RAT v1.0, designed to guide comprehensive reporting, and the TMS-RAT v1.1, a subset of 50 items with the highest inter-rater (overall AC1 = 0.78, range = [0.60-0.99]) and test-retest reliability (overall AC1 = 0.82, range = [0.65-1.0]), intended for retrospective evaluation of reporting in systematic reviews, meta-analyses. ConclusionThe TMS-RAT is a comprehensive, reliable tool that seeks to improve transparency and reproducibility in TMS research.

neuroscience↗

bioRxiv2025

Two parallel lineage-committed progenitors contribute to the developing brain

The hindbrain is a life-sustaining brain region. In one model, a common neural progenitor generates all brain regions. Here our studies of mouse embryos and human pluripotent stem cells (hPSCs) support a different model: two parallel brain progenitors emerge simultaneously during gastrulation, anterior neural ectoderm (forebrain/midbrain progenitor) and posterior neural ectoderm (hindbrain progenitor). Not only are they lineage-committed to respectively form forebrain/midbrain vs. hindbrain in vitro, but they also have diverging chromatin landscapes foreshadowing future forebrain/midbrain vs. hindbrain identities. Leveraging these differences, we differentiated hPSCs into hindbrain rhombomere 5/6-specific motor neurons, hitherto difficult to generate in vitro. We postulate the brain is a composite organ emanating from two lineage-restricted progenitors; these dual progenitors may be evolutionarily conserved across 550 million years from hemichordates to mammals.

developmental biology↗

bioRxiv2025

Antero-posterior patterning in the brittle star Amphipholis squamata and the evolution of body plans across echinoderms

Although the adult pentaradial body plan of echinoderms evolved from a bilateral ancestor, identifying axial homologies between the morphologically divergent echinoderms and their bilaterian relatives has been an enduring problem in zoology. The expression of conserved bilaterian patterning genes in echinoderms provides a molecular framework for resolving this puzzle. Recent studies in juvenile asteroids suggest that the bilaterian antero-posterior axis maps onto the medio-lateral axis that is perpendicular to each of the five rays of the pentaradial body plan. Here we test this hypothesis in another echinoderm class, the ophiuroids, using the cosmopolitan brittle star Amphipholis squamata. Our results show that the general principles of axial patterning are similar to those described in asteroids, and comparisons with existing molecular data from other echinoderm taxa support the idea that medio-lateral deployment of the AP patterning program across the rays predates the evolution of the asterozoan and likely the echinoderm crown-groups. Our data also reveal expression differences between A. squamata and asteroids, which we attribute to secondary modifications specific to ophiuroids. Together, this work provides important comparative data to reconstruct the evolution of axial properties in echinoderm body plans.

evolutionary biology↗

bioRxiv2024

See-Star: a versatile hydrogel-based protocol for clearing large, opaque and calcified marine invertebrates

Studies of morphology and developmental patterning in adult stages of many invertebrates are hindered by opaque structures, such as shells, skeletal elements, and pigment granules that block or refract light and necessitate sectioning for observation of internal features. An inherent challenge in studies relying on surgical approaches is that cutting tissue is semi-destructive, and delicate structures, such as axonal processes within neural networks, are computationally challenging to reconstruct once disrupted. To address this problem, we developed See-Star, a hydrogel-based tissue clearing protocol to render the bodies of opaque and calcified invertebrates optically transparent while preserving their anatomy in an unperturbed state, facilitating molecular labeling and observation of intact organ systems. The resulting protocol can clear large (>1 cm3) specimens to enable deep-tissue imaging, and is compatible with molecular techniques, such as immunohistochemistry and in situ hybridization to visualize protein and mRNA localization. To test the utility of this method, we performed a whole mount imaging study of intact nervous systems in juvenile echinoderms and molluscs, and demonstrate that See-Star allows for comparative studies to be extended far into development facilitating insights into the anatomy of juveniles and adults that are usually not amenable to whole mount imaging.

developmental biology↗

bioRxiv2023

Chromosome-level genome assemblies of two hemichordates provide new insights into deuterostome origin and chromosome evolution

Deuterostomes are an animal superphylum that includes Hemichordata and Echinodermata (together Ambulacraria) and Chordata. The diversity of deuterostome body plans has made it challenging to reconstruct their ancestral condition and to decipher the genetic changes that drove the diversification of deuterostome lineages. Here, we generate chromosome-level genome assemblies of two hemichordate species, Ptychodera flava and Schizocardium californicum, and use comparative genomic approaches to infer the chromosomal architecture of the deuterostome common ancestor and delineate lineage-specific chromosomal modifications. We show that hemichordate chromosomes (1N=23) exhibit remarkable chromosome-scale macrosynteny when compared to other deuterostomes, and can be derived from 24 deuterostome ancestral linkage groups (ALGs). These deuterostome ALGs in turn match previously inferred bilaterian ALGs, consistent with a relatively short transition from the last common bilaterian ancestor to the origin of deuterostomes. Based on this deuterostome ALG complement, we deduced chromosomal rearrangement events that occurred in different lineages. For example, a fusion-with-mixing event produced an Ambulacraria-specific ALG that subsequently split into two chromosomes in extant hemichordates, while this homologous ALG further fused with another chromosome in sea urchins. Orthologous genes distributed in these rearranged chromosomes are enriched for functions in various developmental processes. We found that the deeply conserved Hox clusters are located in highly rearranged chromosomes but have lower densities of transposable elements within the clusters. We also provide evidence that the deuterostome-specific pharyngeal gene cluster was established via the combination of three pre-assembled microsyntenic blocks. We suggest that since chromosomal rearrangement events and formation of new gene clusters may change the regulatory controls of developmental genes, these events may have contributed to the evolution of diverse body plans among deuterostomes.

evolutionary biology↗

bioRxiv2023

Molecular evidence of anteroposterior patterning in adult echinoderms

The origin of the pentaradial body plan of echinoderms from a bilateral ancestor is one of the most enduring zoological puzzles. Since echinoderms are defined by morphological novelty, even the most basic axial comparisons with their bilaterian relatives are problematic. Here, we used conserved antero-posterior (AP) axial molecular markers to determine whether the highly derived adult body plan of echinoderms masks underlying patterning similarities with other deuterostomes. To revisit this classical question, we used RNA tomography and in situ hybridizations in the sea star Patiria miniata to investigate the expression of a suite of conserved transcription factors with well-established roles in the establishment of AP polarity in bilaterians. We find that the relative spatial expression of these markers in P. miniata ambulacral ectoderm shows similarity with other deuterostomes, with the midline of each ray representing the most anterior territory and the most lateral parts exhibiting a more posterior identity. Interestingly, there is no ectodermal territory in the sea star that expresses the characteristic bilaterian trunk genetic patterning program. This suggests that from the perspective of ectoderm patterning, echinoderms are mostly head-like animals, and prompts a reinterpretation of the evolutionary trends that made echinoderms the most derived animal group.

developmental biology↗

bioRxiv2023

Molecular characterization of nervous system organization in the hemichordate Saccoglossus kowalevskii

Hemichordates are an important group for investigating the evolution of bilaterian nervous systems. As the closest chordate outgroup with a bilaterally symmetric adult body plan, hemichordates are particularly informative for exploring the origins of chordates. Despite the importance of hemichordate neuroanatomy for testing hypotheses on deuterostome and chordate evolution, adult hemichordate nervous systems have not been comprehensively described using molecular techniques, and classic histological descriptions disagree on basic aspects of nervous system organization. A molecular description of hemichordate nervous system organization is important for both anatomical comparisons across phyla and for attempts to understand how conserved gene regulatory programs for ectodermal patterning relate to morphological evolution in deep time. Here, we describe the basic organization of the adult hemichordate Saccoglossus kowalevskii nervous system using immunofluorescence, in situ hybridization, and transgenic reporters to visualize neurons, neuropil, and key neuronal cell types. Consistent with previous descriptions, we found the S. kowalevskii nervous system consists of a pervasive nerve plexus that is concentrated in the anterior, along with nerve cords on both the dorsal and ventral sides. Neuronal cell types exhibited clear anteroposterior and dorsoventral regionalization in multiple areas of the body. We observed spatially demarcated expression patterns for many genes involved in synthesis or transport of neurotransmitters and neuropeptides but did not observe clear distinctions between putatively centralized and decentralized portions of the nervous system. In the trunk, there is a clear division of cell types between the dorsal and ventral cords suggesting differences in function. The plexus shows regionalized structure and is consistent with the proboscis base as a major site for information processing rather than the dorsal nerve cord. The absence of neural processes crossing the basement membrane into muscle and extensive axonal varicosities suggest that volumetric transmission may play an important role in neural function. These data now facilitate more informed neural comparisons between hemichordates and other groups and contribute to broader debates on the origins and evolution of bilaterian nervous systems.

evolutionary biology↗

bioRxiv2022

Comparisons of cell proliferation and cell death across life histories in the hemichordate Schizocardium californicum

BackgroundThere are a wide range of developmental strategies in animal phyla, but most insights into adult body plan formation come from direct-developing species. For indirect-developing species, there are distinct larval and adult body plans that are linked together by metamorphosis. Some outstanding questions in indirect-developing organisms include the extent to which larval tissue undergoes cell death during the process of metamorphosis and when the tissue that will give rise to the adult originates. Here we present patterns of cell proliferation and cell death during larval development, metamorphosis, and adult body plan formation, in the hemichordate Schizocardium californium to answer these questions. ResultsWe identified distinct patterns of cell proliferation between larval and adult body plan formation of S. californicum. We found that some adult tissues proliferate prior to the start of any morphological metamorphosis. Additionally, we describe a genetic signature of proliferative cells with an irradiation approach that revealed markers shared between the life history states and others that are unique to larvae or juveniles. Finally, we observed that cell death is minimal in larval stages but begins with the onset of metamorphosis. ConclusionsCell proliferation during the development of S. californicum has distinct patterns in the formation of larval and adult body plans. However, cell death is very limited in larvae and begins during the onset of metamorphosis and into early juvenile development in specific domains. The populations of cells that proliferate and give rise to the larva and juvenile have a genetic signature that is more suggestive of a heterogeneous pool of proliferative progenitors versus a population of pluripotent set-aside cells. Taken together, we propose that S. californicum has a transformative metamorphosis that may be more representative of the development strategies that characterize metamorphosis in many metazoan animals.

developmental biology↗

bioRxiv2020

A single origin of animal excretory organs

Excretion is an essential physiological process, carried out by all living organisms regardless of their size or complexity(1-3). Most animals, which include both protostomes (e.g. flies, flatworms) and deuterostomes (e.g. humans, sea urchins) (together Nephrozoa(4, 5)), possess specialized excretory organs. Those organs exhibit an astonishing diversity, ranging from units composed of just three distinct cells (e.g. protonephridia) to complex structures, built by millions of cells of multiple types with divergent morphology and function (e.g. vertebrate kidneys)(6, 7). Although some molecular similarities between the development of kidneys of vertebrates and the regeneration of the protonephridia of flatworms have been reported(8, 9), the molecular development of nephrozoan excretory organs has never been systematically studied in a comparative context(6). Here we show that a set of highly conserved transcription factors and structural proteins is expressed during the development of excretory organs of six species that represent major protostome lineages and non-vertebrate deuterostomes. We demonstrate that the molecular similarity witnessed in the vertebrate kidney and flatworm protonephridia(8) is also seen in the developing excretory organs of other Nephrozoa. In addition, orthologous structural proteins forming the ultrafiltration apparatus are expressed in all these organs in the filter-forming cells. Our results strongly suggest that excretory organs are homologous and are patterned by the conserved set of developmental genes. We propose that the last common nephrozoan ancestor possessed an ultrafiltration-based, ciliated excretory organ, a structure that later gave rise to the vast diversity of extant excretory organs, including the human kidney. Significance statementMost of the bilaterally symmetrical animals excrete through specialized excretory organs, such as kidneys and nephridia. However, due to the morphological diversity of these organs, it remains unknown whether those structures evolved from a common ancestral organ or appeared several times independently during evolution. In order to answer the question about the origin of excretory organs we investigated the molecular pathways and structural genes involved in the development of nephridia in 6 animal species representing major evolutionary lineages. We show that diverse excretory organs share an ancient molecular patterning and structural molecules. Our results provide strong evidence that all excretory organs originated from a single, simple organ that performed urine production by ultrafiltration in deep geological past.

evolutionary biology↗

bioRxiv2019

Molecular patterning during the development of Phoronopsis harmeri reveals similarities to rhynchonelliform brachiopods

BackgroundAnswering the question how conserved patterning systems are across evolutionary lineages requires a broad taxon sampling. Phoronid development has previously been studied using fate mapping and morphogenesis, yet molecular descriptions are missing. Here we report the expression patterns of the evolutionarily conserved anterior (otx, gsc, six3/6, nk2.1), posterior (cdx, bra) and endomesodermal (foxA, gata4/5/6, twist) markers in the phoronid Phoronopsis harmeri.\n\nResultsThe transcription factors foxA, gata4/5/6 and cdx show conserved expression in patterning the development and regionalization of the phoronid embryonic gut, with foxA expressed in the presumptive foregut, gata4/5/6 demarcating the midgut and cdx confined to the hindgut. Surprisingly, brachyury, an evolutionary conserved transcription factor often associated with gastrulation movements and patterning of the mouth and hindgut, seems to be unrelated with gastrulation and mouth patterning in phoronids. Furthermore, six3/6, a well-conserved anterior marker, shows a remarkably dynamic expression, demarcating not only the apical organ and the oral ectoderm, but also clusters of cells of the developing midgut and the anterior mesoderm, similar to what has been reported for brachiopods, bryozoans and some deuterostome Bilateria.\n\nConclusionsOur comparison of gene expression patterns with other studied Bilateria reveals that the timing of axis determination and cell fate distribution of the phoronid shows highest similarities to rhynchonelliform brachiopods. Despite these similarities, the phoronid P. harmeri shows also particularities in its development, which hint to divergences in the arrangement of gene regulatory networks responsible for germ layer formation and axis specification.

developmental biology↗