
ダクト1とダクト2は、Wntシグナル伝達経路を調節することで、収束伸長と顔面形態形成を制御する。


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Wnt signaling plays crucial roles in embryonic patterning including the regulation of convergent extension during gastrulation, the establishment of the dorsal axis, and later, craniofacial morphogenesis. Further, Wnt signaling is a crucial regulator of craniofacial morphogenesis. The adapter proteins Dact1 and Dact2 modulate the Wnt signaling pathway through binding to Disheveled. However, the distinct relative functions of Dact1 and Dact2 during embryogenesis remain unclear. We found that dact1 and dact2 genes have dynamic spatiotemporal expression domains that are reciprocal to one another suggesting distinct functions during zebrafish embryogenesis. Both dact1 and dact2 contribute to axis extension, with compound mutants exhibiting a similar convergent extension defect and craniofacial phenotype to the wnt11f2 mutant. Utilizing single-cell RNAseq and an established noncanonical Wnt pathway mutant with a shortened axis (gpc4), we identified dact1/2 specific roles during early development. Comparative whole transcriptome analysis between wildtype and gpc4 and wildtype and dact1/2 compound mutants revealed a novel role for dact1/2 in regulating the mRNA expression of the classical calpain capn8. Over-expression of capn8 phenocopies dact1/2 craniofacial dysmorphology. These results identify a previously unappreciated role of capn8 and calcium-dependent proteolysis during embryogenesis. Taken together, our findings highlight the distinct and overlapping roles of dact1 and dact2 in embryonic craniofacial development, providing new insights into the multifaceted regulation of Wnt signaling.

### Competing Interest Statement

The authors have declared no competing interest.

Genetic requirement of dact1/2 to regulate noncanonical Wnt signaling and calpain 8 during embryonic convergent extension and craniofacial morphogenesis

ノンカノニカルwntシグナル伝達とカルパイン8発現を調整することによる収束伸長と顔面形態形成の調節


ノンカノニカルWntシグナル伝達とカルパイン8発現を調整することによる収束伸長と顔面形態形成の調節


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精原細胞は生後早期から成体期にかけて、大規模なクロマチン再構築を経験し、これは遺伝子発現プロファイルの違いや転写因子の結合モチーフの富化と部分的に相関する。


In mammals, spermatogonial cells (SPGs) are undifferentiated male germ cells in testis that are quiescent until birth and then self-renew and differentiate to produce spermatogenic cells and functional sperm from early postnatal life throughout adulthood. The transcriptome of SPGs is highly dynamic and timely regulated during postnatal development. We examined if such dynamics involves changes in chromatin organization by profiling the transcriptome and chromatin accessibility of SPGs from early postnatal stages to adulthood in mice using deep RNA-seq, ATAC-seq and computational deconvolution analyses. By integrating transcriptomic and epigenomic features, we show that SPGs undergo massive chromatin remodeling during postnatal development that partially correlates with distinct gene expression profiles and transcription factors (TF) motif enrichment. We identify genomic regions with significantly different chromatin accessibility in adult SPGs that are marked by histone modifications associated with enhancers and promoters. Some of the regions with increased accessibility correspond to transposable element subtypes enriched in multiple TFs motifs and close to differentially expressed genes. Our results underscore the dynamics of chromatin organization in developing germ cells and complement existing datasets on SPGs by providing maps of the regulatory genome at high resolution from the same cell populations at early postnatal, late postnatal and adult stages collected from single individuals.

### Competing Interest Statement

The authors have declared no competing interest.

Dynamics of transcriptional programs and chromatin accessibility in mouse spermatogonial cells from early postnatal to adult life

マウス精原細胞の転写体とエピゲノムの特徴付けにより-生後と成体精巣における独特のクロマチン制御ランドスケープが明らかになった


マウス精原細胞の転写体とエピゲノムの特徴付けにより、生後と成体精巣における独特のクロマチン制御ランドスケープが明らかになった



HvNotchは、ハイドラの頭部再生において、触手システムを制限する側方抑制プロセスを調整することで、二つの独立したパターン形成システムを協調させる。


Wnt- and Notch signaling pathways are involved in regulating Hydra head regeneration. The Notch-inhibitor DAPT blocks expression of transcriptional repressor genes including CnGsc and HyHes and attenuates hypostomal HyWnt3 - and HyBMP2/4 expression in regenerating Hydra heads while increasing expression of HyBMP5/8b and the c-fos-related gene HyKayak . Inhibition of the transcriptional activity of β-catenin blocks expression of HyAlx during Hydra head regeneration and prevents formation of tentacles, however hypostome regeneration and Wnt3 expression patterns remain intact. This indicates competing pathways for hypostome and tentacle regeneration. We tested this hypothesis on fresh water polyps of Craspedacusta, which do not have tentacles and thus after head removal only regenerate a hypostome with a crescent of nematocytes around the mouth opening. We found that head regeneration in Craspedacusta was inhibited by the β-catenin-inhibitor iCRT14, but not by the Notch-inhibitor DAPT, indirectly confirming that in Hydra Notch-signaling maybe needed to balance separate signaling modules for hypostome and tentacle formation, involving Wnt3/BMP2/4 or HyAlx/HyBMP5/8b expression, respectively. We suggest that during head regeneration, Notch works by inhibiting HyBMP5/8b expression and HyKayak mediated repression of HyWnt3 , rather than directly activating transcription at the HyWnt3 promoter . We thus conclude that HvNotch mediates between two pattern forming systems in Hydra by coordinating a lateral inhibition process restricting the tentacle system.

### Competing Interest Statement

The authors have declared no competing interest.

HvNotch coordinates two independent pattern forming systems during head regeneration in Hydra by supporting a lateral inhibition process restricting the tentacle system

ハイドラの頭部再生過程において-hvnotchが二つの独立したパターン形成システムを調整する


ハイドラの頭部再生過程において、HvNotchが二つの独立したパターン形成システムを調整する



農業革命に伴う澱粉質の高い食事への移行が、アミラーゼ遺伝子の複製数の増加をもたらし、これが人類の適応に寄与してきた。


The impact of structural variation on the evolution of the amylase genes is explored using human pangenome resources and ancient DNA data.

Recurrent evolution and selection shape structural diversity at the amylase locus - Nature

農業革命が人類の遺伝子に及ぼした影響-アミラーゼ遺伝子の構造多様性の進化と選択


農業革命が人類の遺伝子に及ぼした影響 - アミラーゼ遺伝子の構造多様性の進化と選択



マウスの精子フックは、雌性生殖器内での精子の移動と自己組織化行動を促進する重要な役割を果たしている。


In most murine species, spermatozoa exhibit a falciform apical hook at the head end. The function of the sperm hook is not yet clearly understood. In this study, we investigate the role of the sperm hook in the migration of spermatozoa through the female reproductive tract in Mus musculus (C57BL/6), using a deep tissue imaging custom-built two-photon microscope. Through live reproductive tract imaging, we found evidence indicating that the sperm hook aids in the attachment of spermatozoa to the epithelium and facilitates interactions between spermatozoa and the epithelium during migration in the uterus and oviduct. We also observed synchronised sperm beating, which resulted from the spontaneous unidirectional rearrangement of spermatozoa in the uterus. Based on live imaging of spermatozoa-epithelium interaction dynamics, we propose that the sperm hook plays a crucial role in successful migration through the female reproductive tract by providing anchor-like mechanical support and facilitating interactions between spermatozoa and the female reproductive tract in the house mouse.

### Competing Interest Statement

The authors have declared no competing interest.

The sperm hook in house mice: a functional adaptation for migration and self-organised behaviour

マウスの精子フックの機能-雌性生殖器内での移動と自己組織化行動のための適応


マウスの精子フックの機能:雌性生殖器内での移動と自己組織化行動のための適応



昆虫の変態過程では、miR-277/34クラスターのメンバーが雌雄で異なる遺伝子経路を制御することで、性別差を生み出している。


Insects comprise the majority of all described animal species and dominate the terrestrial habitats. The evolution of insect metamorphosis played a profound role in their successful adaptation and radiation. Insect metamorphosis is dependent on hormones ecdysteroids and sesquiterpenoids such as juvenile hormone. Despite the fact there are genuine differences between sexes during insect metamorphosis which facilitate their successful mating, how such sexual dimorphism in metamorphosis is being controlled is poorly known. We first generated transcriptomic profiles of male and female flies in late larvae and early pupae stages. Using a combination of genome-wide prediction and in vitro dual-luciferase validations, members of a microRNA cluster miR-277/34 were found to potentially regulate the neuropeptide receptor ( AstC-R1 ) that when activated inhibits the sesquiterpenoid pathway and a juvenile hormone-dependent transcription factor ( Kr-h1 ) in fly Drosophila melanogaster. Loss-of-function mutants were created deleting either miR-277 or miR-34, and expression levels of both AstC-R1 and Kr-h1 as well as ecdysteroid and sesquiterpenoid hormone titres were altered. Further comparison of transcriptomes of the late larvae and early pupae of both sexes revealed differential gene pathways being regulated by members of miR-277/34 between sexes during metamorphosis. This study highlights how members of a microRNA cluster control hormonal and developmental gene pathways in different sexes of insects during metamorphosis.

### Competing Interest Statement

The authors have declared no competing interest.

Insect metamorphosis is regulated differently between sexes by members of a microRNA cluster

昆虫の変態は性別によって異なる方法で制御されている


ホヤの変態開始には、刺激性Gタンパク質シグナリングと抑制性Gタンパク質シグナリングの相互作用によるcAMP蓄積が重要である。


Larvae of the ascidian Ciona initiate metamorphosis tens of minutes after adhesion to a substratum via its adhesive organ. The gap between adhesion and metamorphosis initiation is suggested to ensure the rigidity of adhesion, allowing Ciona to maintain settlement after losing locomotive activity through metamorphosis. The mechanism producing the gap is unknown. Here, by combining gene functional analyses, pharmacological analyses, and live imaging, we propose that the gap represents the time required for sufficient cAMP accumulation to trigger metamorphosis. Not only the Gs pathway but also the Gi and Gq pathways are involved in the initiation of metamorphosis in the downstream signaling cascade of the neurotransmitter GABA, the known initiator of Ciona metamorphosis. The mutual crosstalk of stimulatory and inhibitory G-proteins functions as the accelerator and brake for cAMP production, ensuring the faithful initiation of metamorphosis at an appropriate time and in the right situation.

### Competing Interest Statement

The authors have declared no competing interest.

Stimulatory and inhibitory G-protein signaling relays drive cAMP accumulation for timely metamorphosis in the chordate Ciona

接着器官への接着時間と強さを測定し-適切な時期に変態を開始するメカニズム


接着器官への接着時間と強さを測定し、適切な時期に変態を開始するメカニズム



逆位多型は、生存と雄の表示形質の間でトレードオフを示す対立的な形質を維持することで、長期的に維持される可能性がある。


Chromosomal inversion polymorphisms can be common, but the causes of their persistence are often unclear. We propose a model for the maintenance of inversion polymorphism, which requires that some variants contribute antagonistically to two phenotypes, one of which has negative frequency-dependent fitness. These conditions yield a form of frequency-dependent disruptive selection, favoring two predominant haplotypes segregating alleles that favor opposing antagonistic phenotypes. An inversion associated with one haplotype can reduce the fitness load incurred by generating recombinant offspring, reinforcing its linkage to the haplotype and enabling both haplotypes to accumulate more antagonistic variants than expected otherwise. We develop and apply a forward simulator to examine these dynamics under a tradeoff between survival and male display. These simulations indeed generate inversion-associated haplotypes with opposing sex-specific fitness effects. Antagonism strengthens with time, and can ultimately yield karyotypes at surprisingly predictable frequencies, with striking genotype frequency differences between sexes and between developmental stages. To test whether this model may contribute to well-studied yet enigmatic inversion polymorphisms in Drosophila melanogaster , we track inversion frequencies in laboratory crosses to test whether they influence male reproductive success or survival. We find that two of the four tested inversions show significant evidence for the tradeoff examined, with In(3R)K favoring survival and In(3L)Ok favoring male reproduction. In line with the apparent sex-specific fitness effects implied for both of those inversions, In(3L)Ok was also found to be less costly to the viability and/or longevity of males than females, whereas In(3R)K was more beneficial to female survival. Based on this work, we expect that balancing selection on antagonistically pleiotropic traits may provide a significant and underappreciated contribution to the maintenance of natural inversion polymorphism.

### Competing Interest Statement

The authors have declared no competing interest.

Inversions Can Accumulate Balanced Sexual Antagonism: Evidence from Simulations and Drosophila Experiments

性的アンタゴニズムの蓄積によりバランスのとれた逆位多型が維持される可能性-シミュレーションとドロソフィラ実験の証拠


性的アンタゴニズムの蓄積によりバランスのとれた逆位多型が維持される可能性 - シミュレーションとドロソフィラ実験の証拠



アフリカ在住のパピオニン類の繁殖季節性は、年間の降雨量の変動性によって大きく影響を受ける。


At a time when seasonal cycles are increasingly disrupted, the ecology and evolution of reproductive seasonality in tropical vertebrates remains poorly understood. In order to predict how changes in seasonality might affect these animals, it is important to understand which aspects of their diverse patterns of reproductive phenology are linked to either the equally diverse patterns of rainfall seasonality (within-year variations) or instead the marked climatic unpredictability (year-to-year variations) occurring across the intertropical belt. Here, we gather birth and climatic seasonality data from 21 populations of 11 Africa-dwelling primate species from the papionin tribe, occupying a wide range of environments, including equatorial, tropical, temperate and arid climates. We investigate (1) the environmental variations that influence the intensity of reproductive seasonality, and (2) the reproductive stage that is synchronized with increased resource availability. Our results demonstrate wide variation in the intensity of birth seasonality between and within species. Across multiple measures of climatic variation, we found rainfall unpredictability to be the only clear predictor of the intensity of reproductive seasonality across populations, i.e., greater year-to-year variation in the amount of rainfall was associated with lower to no reproductive seasonality. Finally, we identified diverse patterns of reproductive phenology, with the most seasonal breeders generally aligning lactation with the peak in resource availability while other populations show more diverse patterns, where conception, lactation or weaning can all be synchronized with maximal food availability. This study sheds new light on the extent and ecological drivers of flexible reproductive phenology in long-lived tropical mammals, and may even contribute to our understanding of why humans give birth year-round.

### Competing Interest Statement

The authors have declared no competing interest.

Flexible reproductive seasonality in Africa-dwelling papionins is associated with low environmental productivity and high climatic unpredictability

アフリカ在住のパピオニン類の柔軟な繁殖季節性を決める気候要因


C. elegans の世代を超えた病原体回避反応は再現性が低く、実験的な調査には不十分な頑健性がある。


Here we report our attempt to replicate reports of transgenerational epigenetic inheritance in Caenorhabditis elegans . Published results from multiple laboratories show that C. elegans adults and their F1 embryos exposed to the pathogen Pseudomonas aeruginosa show pathogen aversion behavior and a pathogen exposure-dependent increase in daf-7/TGF β reporter gene expression. However, results from one group show persistence of the aversion behavior and elevated daf-7 expression in the F2, F3, and F4 generations. In contrast, we failed to consistently detect either the pathogen avoidance response or elevated daf-7 expression beyond the F1 generation. The experimental methods are well-described, the source materials are readily available, including samples from the reporting laboratory, and we explored a variety of environmental conditions likely to account for lab-to-lab variability. None of these adjustments altered our results. Thus, we conclude that this example of transgenerational epigenetic inheritance lacks the robustness required for reliable experimental replication and investigation.

### Competing Interest Statement

The authors have declared no competing interest.

Irreproducibility of transgenerational learned pathogen-aversion response in C. elegans

c-elegans-の世代を超えた病原体回避反応の再現性がない


C. elegans の世代を超えた病原体回避反応の再現性がない
