Biology subjects

Hirata, T.

Publications and source records attributed to Hirata, T..

18 recordsLinked to original sources

bioRxiv2026

An Exploratory Study of Prefrontal Cortex Activation Related to Golf Putting Performance Under Psychological Pressure: A Functional Near-infrared Spectroscopy Approach

Neurofeedback (NF) is a promising method for helping individuals overcome choking under pressure. Identifying relevant neural biomarkers is crucial for developing effective NF. In this exploratory study, we aimed to investigate changes in prefrontal hemodynamic signals associated with golf-putting performance under psychological pressure using functional near-infrared spectroscopy. Participants engaged in a one-on-one golf-putting task against an experimenter, with monetary rewards introduced to induce psychological pressure. This manipulation successfully elicited psychological pressure, leading to impaired performance in some participants. Based on performance changes between the practice and competition sessions, participants were categorized into a non-choking group (performance improved) and a choking group (performance declined). Statistical analysis revealed significantly greater increases in prefrontal activation from practice to competition in the non-choking group than in the choking group, especially in the left superior frontal gyrus. Furthermore, moderate but statistically nonsignificant negative correlations were observed between changes in activation in this region and changes in putting error, indicating that greater activation increases tended to accompany less performance deterioration or greater performance improvement. These exploratory findings suggest that the left superior frontal gyrus warrants further investigation as a candidate biomarker for NF interventions aimed at mitigating choking under pressure.

neuroscience↗

bioRxiv2026

Phenotype-driven screening reveals a causal role for the cortex in pupil control

Phenotype-driven forward screening offers a powerful strategy to discover neuronal substrates underlying physical and behavioral traits without prior anatomical or functional assumptions. Historically, such approaches have identified many important neuronal circuits using invertebrate model organisms, but application to mammals has remained limited by the lack of appropriate strategies. Here we quantitatively profiled 56 neurological phenotypic features across more than 200 adult mice when neurodevelopmentally classified neurons were activated or inhibited by chemogenetics. This screen yielded a wide spectrum of robust neurological phenotypes. Upon analyzing these phenotypes computationally, we narrowed down to the hypothesis that activation of cortical neurons enlarges pupil size. Experimental evidence using optogenetics and in utero electroporation indicated that this hypothesis is true. Our results provide proof of principle that phenotype-driven forward approach in mammals is a powerful alternative as a laboratory approach to uncover brain substrates, and offers a general framework for systematically mapping neural circuits that regulate physical and behavioral phenotypes.

neuroscience↗

bioRxiv2026

Co-targeting an AMPK--MAPK axis reprograms CAFs and suppresses PDAC

Pancreatic ductal adenocarcinoma (PDAC) is a fatal cancer characterized by limited therapeutic options and a highly treatment-resistant tumor microenvironment. Beyond tumor-intrinsic genetic alterations, growing evidence indicates that host-microbiome interactions influence cancer progression through microbial metabolites. However, how microbiome-derived metabolites influence oncogenic signaling in PDAC remains unclear. Here, integrated profiling revealed a consistent reduction of the microbial metabolite acetic acid in fecal samples from treatment-naive patients with PDAC and in a genetically defined Drosophila model recapitulating key PDAC driver alterations. Acetic acid activates AMP-activated protein kinase, and pharmacological activation of this pathway together with inhibition of mitogen-activated protein kinase signaling suppressed tumor growth in fly and mouse models. Combined pathway targeting restored AMPK activity and suppressed cancer-associated fibroblast activation. These findings identify a microbiome-associated metabolic vulnerability in PDAC and suggest that coordinated targeting of metabolic and oncogenic signaling may restrain tumor progression and improve therapeutic strategies.

cancer biology↗

bioRxiv2025

Dynamic O-GlcNAcylation of Sec23-interacting protein regulates COPII function

About one-third of the eukaryotic proteome transits the secretory pathway to reach its correct cellular or extracellular destination. At the earliest stage, transport from the endoplasmic reticulum (ER) to the ER-Golgi intermediate compartment (ERGIC) or Golgi apparatus is mediated by coat protein complex II (COPII). COPII coats consist of inner and outer layers formed by Sec23-Sec24 heterodimers and Sec13-Sec31 heterotetramers, respectively, which initially assemble at ER exit sites (ERES) to form transport carriers. Sec23-interacting protein (Sec23IP) links the inner and outer coats through its interactions with both Sec23A and Sec31A, positioning it as a key potential regulator of COPII function. However, the mechanisms controlling Sec23IP activity remain poorly understood. Here, we investigate how physiological stimuli regulate COPII function through the dynamic modification of Sec23IP by O-linked {beta}-N-acetylglucosamine (O-GlcNAc), a reversible, intracellular form of glycosylation. We first validated Sec23IP as a bona fide O-GlcNAcylated protein. Rescue experiments in Sec23IP knockout cells with a nearly unglycosylatable mutant protein demonstrated the essential role of O-GlcNAcylation in the intrinsically disordered domain in protein transport and in recruiting Sec31A to ERES. Moreover, O-GlcNAcylation of Sec23IP increased during protein transport, coinciding with a reduction in its interaction with Sec31A. These results indicate that distinct site-specific O-GlcNAcylation of Sec23IP spatiotemporally modulates its association with Sec31A to fine-tune ERES recruitment and COPII assembly/disassembly. Our work provides new insight into Sec23IP regulation and suggests that O-GlcNAc on other COPII proteins may govern carrier formation, uncoating, and transport.

cell biology↗

bioRxiv2025

Dynamic regulation of the COPII interactome and collagen trafficking by site-specific glycosylation of Sec24D

Coat protein complex II (COPII) mediates anterograde trafficking from the endoplasmic reticulum (ER). While the core COPII machinery is well-characterized, how cells regulate COPII to accommodate large cargoes, including collagens, remains incompletely understood. Here, we show that the cargo-selecting COPII subunit Sec24D is modified by site-specific O-linked {beta}-N-acetylglucosamine (O-GlcNAc) in its N-terminal intrinsically disordered region upon induction of collagen transport. These glycosylations are required for collagen trafficking in human cells and developing zebrafish. Crosslinking proteomics demonstrated that each O-GlcNAcylation influences the Sec24D interactome in a distinct way, revealing novel mediators of COPII function. In particular, Sec24D glycosylation is required for its interaction with myoferlin, which unexpectedly facilitates fusion of ER exit sites (ERES) and the ER-Golgi intermediate compartment (ERGIC) to enable collagen transport. Our results establish Sec24D O-GlcNAcylation as a dynamic regulator of COPII protein-protein interactions and collagen trafficking and identify myoferlin as a novel mediator of this process.

cell biology↗

bioRxiv2025

Adaptive Evolution of Gene Regulatory Networks in Mammalian Neocortical Neurons

Mammals have evolved a plethora of adaptations that have enabled them to thrive in diverse environments. Among the most significant is the emergence of a more complex brain, exemplified by the dramatic transformation of the dorsal cortex from a single layer of excitatory projection neurons (ExNs) in ancestors to a multilayered cerebral neocortex enriched with diverse intratelencephalic (IT) and extratelencephalic (ET) ExN subtypes. These ExNs established specialized projection systems, such as the corticospinal tract and corpus callosum, enhancing brain connectivity and functionality. However, the evolutionary mechanisms underlying these mammalian-specific adaptations remain elusive. By comparing the landscape of gene expression and cis-regulatory elements (CREs) in mouse ExN subtypes and by cross-species examination of mammalian and non-mammalian CREs, we identified mammalian-specific CREs and expression patterns. The mammalian-specific CREs include a subset bound by ZBTB18 that are associated with genes defining IT and ET subtypes and connectivity. Both ZBTB18 and these target genes have previously been implicated in intellectual disability and autism. Deletion of Zbtb18 in mouse ExNs dysregulated target gene expression, reduced molecular diversity, diminished corticospinal and callosal projections, and increased intrahemispheric cortico-cortical association projections to the prefrontal cortex, resembling features of non-mammalian dorsal pallium. Interestingly, ZBTB18 binding motifs are highly enriched in callosally projecting IT-biased CREs, where they show higher conservation specifically in mammals. This study uncovers critical components and mammalian-specific evolutionary adaptations within a regulatory node essential for neocortical ExN identity and connectivity, with implications for neurodevelopmental and neuropsychiatric disorders.

neuroscience↗

bioRxiv2025

Evidence for Functional Regulation of the KLHL3/WNK Pathway by O-GlcNAcylation

The 42-member Kelch-like (KLHL) protein family are adaptors for ubiquitin E3 ligase complexes, governing the stability of a wide range of substrates. KLHL proteins are critical for maintaining proteostasis in a variety of tissues and are mutated in human diseases, including cancer, neurodegeneration, and familial hyperkalemic hypertension. However, the regulation of KLHL proteins remains incompletely understood. Previously, we reported that two KLHL family members, KEAP1 and gigaxonin, are regulated by O-linked {beta}-N-acetylglucosamine (O-GlcNAc), an intracellular form of glycosylation. Interestingly, some ubiquitination targets of KEAP1 and gigaxonin are themselves also O-GlcNAcylated, suggesting that multi-level control by this post-translational modification may influence many KLHL pathways. To test this hypothesis, we examined KLHL3, which ubiquitinates with-no-lysine (WNK) kinases to modulate downstream ion channel activity. Our biochemical and glycoproteomic data demonstrate that human KLHL3 and all four WNK kinases (WNK1-4) are O-GlcNAcylated. Moreover, our results suggest that O-GlcNAcylation affects WNK4 function in both osmolarity control and ferroptosis, with potential implications ranging from blood pressure regulation to neuronal health and survival. This work demonstrates the functional regulation of the KLHL3/WNK axis by O-GlcNAcylation and supports a broader model of O-GlcNAc serving as a general regulator of KLHL signaling and proteostasis.

cell biology↗

bioRxiv2025

Dynamic regulation of Sec24C by phosphorylation and O-GlcNAcylation during cell cycle progression

During mitosis, eukaryotic cells cease anterograde trafficking from the endoplasmic reticulum (ER) towards the Golgi. This cessation corresponds with the dispersal of the COPII transport protein, Sec24C, from juxtanuclear ER exit sites (ERES) into a diffusely cytosolic pool. Redistribution of Sec24 paralogs and other core COPII proteins may underlie the mitotic pause in secretion and may be required for the equal inheritance of endomembrane organelles and machinery by both daughter cells. Therefore, it is important to understand the mechanisms governing the mitotic relocalization of COPII components. Here, we explore the role of post-translational modifications (PTMs) of the model COPII protein Sec24C in this phenotypic switch during mitosis. In interphase, Sec24C is modified by O-linked {beta}-N-acetylglucosamine (O-GlcNAc), and we show that this glycan is rapidly removed upon mitotic entry, influencing the timing of Sec24C dispersal. Additionally, we identify novel, cell cycle phase-enriched phosphorylation events on Sec24C, including phosphosites that regulate the stability and localization of the protein, providing the first systematic characterization of dynamic PTMs on any Sec24 protein. Together, our data support the hypothesis that phosphorylation and glycosylation of Sec24C act in concert to induce rapid dispersal upon mitotic entry and may promote equal partitioning of the endomembrane system to daughter cells after division.

biochemistry↗

bioRxiv2023

A single-cell atlas of transcribed cis-regulatory elements in the human genome

Transcribed cis-regulatory elements (tCREs), such as promoters and enhancers, are fundamental to modulate gene expression and define cell identity. The detailed mapping of tCREs at single-cell resolution is essential for understanding the regulatory mechanisms that govern cellular functions. Prior tCRE catalogs, limited by bulk analysis, have often overlooked cellular heterogeneity. We have constructed a tCRE atlas using single-cell 5-RNA-seq, capturing over 340,000 single-cells from 23 human tissues and annotating more than 175,000 tCREs, substantially enhancing the scope and granularity of existing cis-regulatory element annotations in the human genome. This atlas unveils patterns of gene regulation, revealing connections between broadly expressed promoters and cell type-specific distal tCREs. Assessing trait heritability at single-cell resolution with a novel tCRE module-based approach, we uncovered the nuanced trait-gene regulatory relationships across a continuum of cell populations, offering insights beyond traditional gene-level and bulk-sample analyses. Our study bridges the gap between gene regulation and trait heritability, underscoring the potential of single-cell analysis to elucidate the genetic foundations of complex traits. These insights set the stage for future research to investigate the impact of genetic variations on diseases at the individual level, advancing the understanding of cellular and molecular basis of trait heritability.

genomics↗

bioRxiv2023

HOIL-1L deficiency induces cell cycle alteration which causes immaturity of myocyte and fibrogenesis

HOIL-1L deficiency was recently reported to be one of the causes of myopathy and dilated cardiomyopathy (DCM). However, the mechanisms by which myopathy and DCM develop have not been clearly elucidated. Here, we sought to elucidate these mechanisms using the murine myoblast cell line C2C12 and disease-specific human induced pluripotent stem cells (hiPSCs). Myotubes were differentiated from control and HOIL-1L-KO C2C12 cells. Cardiomyocytes (CMs) were differentiated from control and patient-derived hiPSCs. We investigated the impact of HOIL-1L on differentiation of myotubes and CMs. Myotubes differentiated from HOIL-1L-KO C2C12 cells exhibited deteriorated differentiation and mitotic cell accumulation. CMs differentiaed from patient-derived hiPSCs had an abnormal morphology with a larger size and were excessively multinucleated compared with CMs differentiaed from control hiPSCs. Further analysis of hiPSC- derived CMs showed that HOIL-1L deficiency caused cell cycle alteration and mitotic cell accumulation. These results were supported by RNA sequencing of C2C12 cell-derived myotubes. In addition, SerpinE2, a cardiac fibrogenesis gene, was significantly upregulated in CMs differentiaed from patient-derived hiPSCs. These results demonstrate that abnormal cell maturation and fibrosis possibly contribute to the development of DCM and myopathy. In conclusion, HOIL-1L is an important intrinsic regulator of cell cycle-related myotube and CM maturation and cell proliferation.

cell biology↗

bioRxiv2022

Molecular diversity and connectivity of accessory olfactory system neurons

Olfaction is the primary sensory modality by which most vertebrate species interpret environmental cues for appropriate behavioral outputs. The olfactory system is subdivided into main (MOS) and accessory (AOS) components which process volatile and non-volatile cues. While much is known regarding the molecular diversity of neurons that comprise the MOS, less is known about the AOS. Here, focusing on the AOS which is largely comprised of the peripheral vomeronasal organ (VNO), the accessory olfactory bulb (AOB) and the medial subnucleus of the amygdala (MeA), we studied the molecular diversity and neuronal subtype connectivity of this interconnected circuit. We show that populations of neurons of the AOS can be molecularly subdivided based on their current or prior expression of the transcription factors Foxp2 or Dbx1. We show that the majority of AOB neurons that project directly to the MeA are of the Foxp2-lineage. Using single cell patch clamp electrophysiology, we further reveal that in addition to sex-specific differences across lineage, the relative contributions of excitatory and inhibitory inputs to MeA Foxp2-lineage neurons differ between sexes. Together, this work uncovers a novel molecular diversity of AOS neurons and lineage- and sex-differences in patterns of connectivity.

neuroscience↗

bioRxiv2022

Nhlh1 and Nhlh2, a global transcriptional mechanism regulating commissural axon projection via activating Robo3

SUMMARYCommissural neurons are highly heterogeneous in their developmental origins, neurotransmitter type and function, but all share the common feature of projecting axons across the midline. The floor plate-crossing commissural axons in mammals, from the spinal cord to the midbrain, are guided by a conserved molecular mechanism relying primarily on Netrin-1/DCC/Robo3 signaling. Up to date, we know very little about the upstream transcriptional program that specify commissural axon laterality, neither do we know if a common mechanism operates in all commissural neurons. Here, we identified a pair of highly related helix-loop-helix transcription factors, Nhlh1 and Nhlh2, as a global transcriptional mechanism that controls the laterality of all floor plate-crossing commissural axons. Forced expression of Nhlh1/2 induce ectopic Robo3 expression and contralateral axon projections. And mutant mice deficient in both genes show a remarkable reduction in Robo3 expression and a total lack of ventral commissures from the spinal cord to the midbrain. This global mechanism may interact with neuron type specific mechanism to achieve specific generation of commissural circuits.

neuroscience↗

bioRxiv2020

Synthesis and preclinical evaluation of MTP38 as a novel PET ligand for phophodiesterase 7 in the brain

PurposePhosphodiesterase (PDE) 7 is a potential therapeutic target for neurological and inflammatory diseases, although in-vivo visualization of PDE7 has not been successful. In this study, we aimed to develop [11C]MTP38 as a novel positron emission tomography (PET) ligand for PDE7. Methods[11C]MTP38 was radiosynthesized by 11C-cyanation of a bromo precursor with [11C]HCN. PET scans of rat and rhesus monkey brains and in-vitro autoradiography of brain sections derived from these species were conducted with [11C]MTP38. In monkeys, dynamic PET data were analyzed with an arterial input function to calculate the total distribution volume (VT). The non-displaceable binding potential (BPND) in the striatum was also determined by a reference tissue model with cerebellar reference. Finally, striatal occupancy of PDE7 by an inhibitor was calculated in monkeys according to changes in BPND. Results[11C]MTP38 was synthesized with radiochemical purity [≥] 99.4% and molar activity of 38.6 {+/-} 12.6 GBq/mol. Autoradiography revealed high radioactivity in the striatum and its reduction by non-radiolabeled ligands, in contrast with unaltered autoradiographic signals in other regions. In-vivo PET after radioligand injection to rats and monkeys demonstrated that radioactivity was rapidly distributed to the brain and intensely accumulated in the striatum relative to the cerebellum. Correspondingly, estimated VT values in the monkey striatum and cerebellum were 3.59 and 2.69 mL/cm3, respectively. The cerebellar VT value was unchanged by pretreatment with unlabeled MTP38. Striatal BPND was reduced in a dose-dependent manner after pretreatment with MTP-X, a PDE7 inhibitor. Relationships between PDE7 occupancy by MTP-X and plasma MTP-X concentration could be described by Hills sigmoidal function. ConclusionWe have provided the first successful preclinical demonstration of in-vivo PDE7 imaging with a specific PET radioligand. [11C]MTP38 is a feasible radioligand for evaluating PDE7 in the brain and is currently being applied to a first-in-human PET study.

neuroscience↗

bioRxiv2020

Striped distribution pattern of Purkinje cells of different birthdates in the mouse cerebellar cortex studied with the Neurog2-CreER transgenic line

Heterogeneity of Purkinje cells (PCs) that are arranged into discrete longitudinal stripes in the cerebellar cortex is related to the timing of PC generation. To understand the cerebellar compartmental organization, we mapped the PC birthdate (or differentiation timing) in the entire cerebellar cortex. We used the birthdate-tagging system of neurog2-CreER (G2A) mice hybridized with the AldocV strain which clarifies the zebrin (aldolase C) longitudinal striped pattern. The pattern of the birthdate-dependent PC distribution was arranged consistently into longitudinally-oriented stripes throughout almost all lobules except for the nodulus, paraflocculus and flocculus, in which distinct stripes were observed.Boundaries of the PC birthdate stripes were found either in the middle or coincided with that of the zebrin stripes. PCs in each birthdate stripe were born in various periods between embryonic day (E) 10.0 and E 13.5. In the vermis, PCs were chronologically distributed from lateral to medial stripes. In the paravermis, PCs of early birthdates were distributed in the long lateral zebrin-positive stripe (stripe 4+//5+) and the medially neighboring narrow zebrin-negative substripe (3d-//e2-), while PCs of late birthdates were distributed in the rest of all paravermal areas. In the hemisphere, PCs of early and late birthdates were intermingled in the majority of areas. The results indicate that the birthdate of a PC is a partial determinant for the zebrin compartment in which it is located. However, the correlation between the PC birthdate and the zebrin compartmentalization is not simple, and distinct among the vermis, paravermis, hemisphere, nodulus, and flocculus. HighlightsBirthdates of Purkinje cells (PCs) were mapped on the cerebellar zebrin striped pattern by using Neurog2-CreER (G2A) mice. The vermis, paravermis, hemisphere, nodulus, and flocculus had distinct longitudinally-striped patterns of PC birthdate distribution. PCs in each birthdate stripe were born in various periods between embryonic day (E) 10.0 and E 13.5. Boundaries of PC birthdate distributions were located at the boundaries of zebrin stripes or in the middle of a zebrin stripe. The results indicate that the PC birthdate is a partial determinant for the zebrin compartment in which a PC is located.

neuroscience↗

bioRxiv2019

Cross-talks of glycosylphosphatidylinositol biosynthesis with glycosphingolipid biosynthesis and ER-associated degradation

Glycosylphosphatidylinositol (GPI)-anchored proteins and glycosphingolipids interact with each other in the mammalian plasma membranes, forming dynamic microdomains. How their interaction starts in the cells has been unclear. Here, based on a genome-wide CRISPR-Cas9 genetic screen for genes required for GPI side-chain modification by galactose in the Golgi apparatus, we report that {beta}1,3-galactosyltransferase 4 (B3GALT4), also called GM1 ganglioside synthase, additionally functions in transferring galactose to the N-acetylgalactosamine side-chain of GPI. Furthermore, B3GALT4 requires lactosylceramide for the efficient GPI side-chain galactosylation. Thus, our work demonstrates previously unexpected evolutionary and functional relationships between GPI-anchored proteins and glycosphingolipids in the Golgi. Through the same screening, we also show that GPI biosynthesis in the endoplasmic reticulum (ER) is severely suppressed by ER-associated degradation to prevent GPI accumulation when the transfer of synthesized GPI to proteins is defective. Our data demonstrates cross-talks of GPI biosynthesis with glycosphingolipid biosynthesis and the ER quality control system.

cell biology↗

bioRxiv2019

Complement- and inflammasome-mediated autoinflammation-paroxysmal nocturnal hemoglobinuria

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hematopoietic stem cell disorder characterized by complement-mediated hemolysis and thrombosis, and bone marrow failure. Affected cells harbor somatic mutation in X-linked PIGA gene, essential for the initial step in glycosylphosphatidylinositol (GPI) biosynthesis. Loss of GPI biosynthesis results in defective cell-surface expression of GPI-anchored complement regulators CD59 and DAF. The affected stem cells generate many abnormal blood cells after clonal expansion, which occurs under bone marrow failure. Here, we report the mechanistic basis of a disease entity, autoinflammation-paroxysmal nocturnal hemoglobinuria (AIF-PNH), caused by germline mutation plus somatic loss of PIGT on chromosome 20q. A region containing maternally imprinted genes implicated in clonal expansion in 20q-myeloproliferative syndromes was lost together with normal PIGT from paternal chromosome 20. Taking these findings together with a lack of bone marrow failure, the mechanisms of clonal expansion in AIF-PNH appear to differ from those in PNH. AIF-PNH is characterized by intravascular hemolysis and recurrent autoinflammation, such as urticaria, arthralgia, fever and aseptic meningitis. Consistent with PIGTs essential role in synthesized GPIs attachment to precursor proteins, non-protein-linked free GPIs appeared on the surface of PIGT-defective cells. PIGT-defective THP-1 cells accumulated higher levels of C3 fragments and C5b-9 complexes, and secreted more IL-1{beta} than PIGA-defective cells after activation of the complement alternative pathway. IL-1{beta} secretion was dependent upon C5b-9 complexes, accounting for the effectiveness of the anti-C5 drug eculizumab for both intravascular hemolysis and autoinflammation. These results suggest that free GPIs enhance complement activation and inflammasome-mediated IL-1{beta} secretion.

immunology↗

bioRxiv2018

A survey of public attitudes towards third-party reproduction in Japan in 2014

Objective: The objective of this study was to examine public attitudes towards third-party reproduction and the disclosure of conception through third-party reproduction.\n\nMethods: We conducted the web-based survey for the public attitude towards third-party reproduction in February 2014. Twenty-five hundred people were recruited with equal segregation of age (20s, 30s, 40s, and 50s) and gender. We analyzed the association between gender, age, infertility, and ethical view using a questionnaire regarding donor sperm, donor oocyte, donor embryo, gestational surrogacy, and disclosure to offspring.\n\nResults: Of the respondents, 36.2% approved and 26.6% disapproved with gamete or embryo donation. The frequency of those who approved was the lowest in females in the 50-59 years age group, and was significantly higher in males or females with infertility. Secondly, 40.9% approved and 21.8% disapproved with gestational surrogacy. The frequency of those who approved gestational surrogacy was higher in males or females with infertility. Thirdly, 46.3% of respondents agreed and 20.4% disagreed with \"offspring have the right to know their origin\". Those who disagreed were primarily in the 50-59 age group of both genders, and disagreement was significantly higher in the infertility group compared with non-infertility group.\n\nConclusion: In this study, public attitudes were affected by gender, age, and experience of infertility. These study findings are important in understanding the attitude towards third-party reproduction and disclosure to the offspring. Respondents having indecisive attitudes were >30%, which might indicate an increased requirement for information and education to enhance the discussion on the ethical consensus on third-party reproduction in Japan.

scientific communication and education↗

bioRxiv2017

Frequent Non-random Shifts in the Temporal Sequence of Developmental Landmark Events during Fish Evolutionary Diversification

Morphological transformations can be generated by evolutionary changes in the sequence of developmental events. In this study, we examined the evolutionary dynamics of the developmental sequence on a macroevolutionary scale using the teleost. Using the information from previous reports describing the development of 31 species, we extracted the developmental sequences of 19 landmark events involving the formation of phylogenetically conserved body parts; we then inferred ancestral developmental sequences by two different parsimony-based methods--event-pairing (Jeffery, Bininda-Emonds, Coates & Richardson, 2002a) and continuous analysis (Germain & Laurin, 2009). The phylogenetic comparisons of these sequences revealed event-dependent heterogeneity in the frequency of sequence changes. Most of the sequence changes occurred as exchanges of temporally neighboring events. The phylogenetic analyses suggested that the ancestral species had experienced frequent changes in developmental sequences. Although the analyses showed that these heterochronic changes accumulated along phylogenic time, the precise distribution of the changes over the teleost phylogeny remains unclear due to technical limitations. Finally, this first comprehensive analysis of teleost developmental sequences will provide solid ground on which to elucidate the significance of developmental timing in animal morphological diversification.

evolutionary biology↗