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To provide context for the diversification of archosaurs-the group that includes crocodilians, dinosaurs, and birds-we generated draft genomes of three crocodilians: Alligator mississippiensis (the American alligator), Crocodylus porosus (the saltwater crocodile), and Gavialis gangeticus (the Indian gharial). We observed an exceptionally slow rate of genome evolution within crocodilians at all levels, including nucleotide substitutions, indels, transposable element content and movement, gene family evolution, and chromosomal synteny. When placed within the context of related taxa including birds and turtles, this suggests that the common ancestor of all of these taxa also exhibited slow genome evolution and that the comparatively rapid evolution is derived in birds. The data also provided the opportunity to analyze heterozygosity in crocodilians, which indicates a likely reduction in population size for all three taxa through the Pleistocene. Finally, these data combined with newly published bird genomes allowed us to reconstruct the partial genome of the common ancestor of archosaurs, thereby providing a tool to investigate the genetic starting material of crocodilians, birds, and dinosaurs.

Progress in evolutionary developmental biology (evo‐devo) has deepened our understanding of how intrinsic properties of embryogenesis, along with natural selection and population genetics, shape phenotypic diversity. A focal point of recent empirical and theoretical research is the idea that highly developmentally stable phenotypes are more conserved in evolution. Previously, we demonstrated that in Japanese medaka (Oryzias latipes), embryonic stages and genes with high stability, estimated through whole‐embryo RNA‐seq, are highly conserved in subsequent generations. However, the precise origin of the stability of gene expression levels evaluated at the whole‐embryo level remained unclear. Such stability could be attributed to two distinct sources: stable intracellular expression levels or spatially stable expression patterns. Here we demonstrate that stability observed in whole‐embryo RNA‐seq can be attributed to stability at the cellular level (low variability in gene expression at the cellular levels). We quantified the intercellular variations in expression levels and spatial gene expression patterns for seven key genes involved in patterning dorsoventral and rostrocaudal regions during early development in medaka. We evaluated intracellular variability by counting transcripts and found its significant correlation with variation observed in whole‐embryo RNA‐seq data. Conversely, variation in spatial gene expression patterns, assessed through intraindividual left–right asymmetry, showed no correlation. Given the previously reported correlation between stability and conservation of expression levels throughout embryogenesis, our findings suggest a potential general trend: the stability or instability of developmental systems—and the consequent evolutionary diversity—may be primarily anchored in intrinsic fundamental elements such as the variability of intracellular states. Research highlights: We investigated the precise origins of developmental stability that was previously determined by whole‐embryo RNA‐seq, given its significance in indicating the potential for phenotypic conservation during evolution.Our findings suggest that the developmental stability can be primarily attributed to stability in gene expression at the cellular level, rather than stability in spatial gene expression patterns.The result provides further insight into how embryogenesis introduces bias in phenotypic evolution, and thus paves the way for a deeper understanding of developmental stability that would enable the prediction of phenotypic evolution. [ABSTRACT FROM AUTHOR]

Maternal microchimerism (MMc) is the phenomenon that a low number of cells from the mother persists within her progeny. Despite their regular presence in mammalian pregnancies, the overall cell type repertoire and roles of maternal cells, especially after birth, remain unclear. By using transgenic mouse strains and human umbilical blood samples, recent studies have for the first time characterized and quantified MMc cell type repertoires in offspring, identified the cross‐generational influence on fetal immunity, and determined possible factors that affect their presence in offspring. This review summarizes new findings, especially on the maternal cell type repertoires and their potential role in utero, in postnatal life, and long after birth. [ABSTRACT FROM AUTHOR]

A new design approach for implemented with a bit-serial adder for high-throughput arithmetic circuits based on state transitions using single-flux-quantum (SFQ) logic circuits which demonstrates 36-MHz operations speed is presented.

Morphogenesis of the heart requires development of the endocardial cushion tissue that gives rise to the membranous septa and valves. Here we show that Meltrin [beta]/ADAM19, a novel metalloprotease-disintegrin, participates in the development of the endocardial cushion. Mice lacking Meltrin [beta] exhibit ventricular septal defect (VSD) and immature valves, and most of the animals die soon after birth. During development of the endocardial cushion, epithelial--mesenchymal transformation (EMT) of endocardial epithelial cells generates most of the cushion mesenchymes that constitute the main components of the septa and valves. Meltrin [beta] is expressed in both the epithelia and the mesenchymes of the endocardial cushion. In the absence of Meltrin [beta], the cushion is small or thin in the septum-forming region and show poor remodeling of cardiac jelly components; both of these characteristics suggest impaired growth and differentiation of the endocardial cushion. When embryonic fibroblasts are cultured sparsely, Meltrin [beta]-lacking cells exhibit aberrant ectodomain shedding of type I Neuregulin, one of the ErbB ligands expressed in endocardial cells. These results suggest the necessity of proteolytic regulation of ErbB ligands by Meltrin [beta] for proper heart development. Keywords: Metalloprotease; Disintegrin; ErbB; Neuregulin; Knockout mouse; VSD; Endocardial cushion

To understand Haeckel's idea of recapitulation with modern evolutionary biology, one has to realize how evolutionarily conserved embryonic stages appear sequentially in developmental processes as chains of causality. Whether the idea of evolution was accepted or not, Haeckel and von Baer commonly saw an importance of a particularly conserved mid‐embryonic stage in biphasic development of metazoans, the phylotype, that defines an animal phylum as the developmental source of a basic body plan. In an evolutionary context, the phylotypic stage was once understood by Haeckel to reflect the common ancestor of animal phyla, which went through hypermorphosis independently into various phyla. Recent comprehensive molecular studies, however, accumulated data to refute this idea. The conserved embryonic pattern does not reflect an ancestral adult morphology but appears to have arisen primarily as an embodiment of developmental constraints established through evolutionary processes. How the developmental burden results in a nested series of constraints will solve the recapitulative tendency of developmental programs. Research Highlights: This review is primarily focused on the possible evolutionary mechanism that resulted in a recapitulation‐like sequence of developmental processes. Theory of developmental burden by Riedl (1978) may explain why evolutionarily new traits tend to appear after the establishment of ancestral patterns in development. This ancestral pattern, however, does not resemble adult forms of ancestors, but more likely reflect ancestral developmental constraints, which is consistent with recent transcriptome data. [ABSTRACT FROM AUTHOR]

The notochord functions primarily as a supporting tissue to maintain the anteroposterior axis of primitive chordates, a function that is replaced entirely by the vertebral column in many vertebrates. The notochord still appears during vertebrate embryogenesis and plays a crucial role in the developmental pattern formation of surrounding structures, such as the somites and neural tube, providing the basis for the vertebrate body plan. The indispensable role of the notochord has often been referred to as the developmental burden and used to explain the evolutionary conservation of notochord; however, the existence of this burden has not been successfully exemplified so far. Since the adaptive value of target tissues appears to result in the evolutionary conservation of upstream structures through the developmental burden, we performed comparative gene expression profiling of the notochord, somites, and neural tube during the mid‐embryonic stages in turtles and chicken to measure their evolutionary conservation. When compared with the somites and neural tube, overall gene expression profiles in the notochord showed significantly lower or merely comparable levels of conservation. However, genes involved in inductive signalings, such as the sonic hedgehog (Shh) cascade and the formation of functional primary cilia, showed relatively higher levels of conservation in all the three structures analyzed. Collectively, these results suggest that shh signals are critical as the inductive source and receiving structures, possibly constituting the inter‐dependencies of developmental burden. Research Highlights: Potential evolutionary effects toward notochord by developmental burden was evaluated by Laser Micro Dissection RNAseq (LMDseq). Notochord was less conserved than neural tube and somites; however, genes in sonic hedgehog (shh) signaling cascade was found to be evolutionarily conserved (not only in notochord but also in somites and neural tube). These results suggest that Shh signals are critical as the inductive source and receiving structures, possibly constituting the inter‐dependencies of developmental burden. Further studies that directly measure the burden required to verify the hypothesis are awaited. [ABSTRACT FROM AUTHOR]

Recapitulation is a hypothetical concept that assumes embryogenesis of an animal parallels its own phylogenetic history, sequentially developing from more ancestral features to more derived ones. This concept predicts that the earliest developmental stage of various animals should represent the most evolutionarily conserved patterns. Recent transcriptome‐based studies, on the other hand, have reported that mid‐embryonic, organogenetic periods show the highest level of conservation (the developmental hourglass model). This, however, does not rule out the possibility that recapitulation would still be detected after the mid‐embryonic period. In accordance with this, recapitulation‐like morphological features are enriched in late developmental stages. Moreover, our recent chromatin accessibility‐based study provided molecular evidence for recapitulation in the mid‐to‐late embryogenesis of vertebrates, as newly evolved gene regulatory elements tended to be activated at late embryonic stages. In this review, we revisit the recapitulation hypothesis, together with recent molecular‐based studies that support the developmental hourglass model. We contend that the recapitulation hypothesis does not entirely contradict the developmental hourglass model and that these two may even coexist in later embryonic stages of vertebrates. Finally, we review possible mechanisms underlying the recapitulation pattern of chromatin accessibility together with the hourglass‐like evolutionary conservation in vertebrate embryogenesis. Research Highlights: Recapitulation pattern has been reported for chromatin accessibility during the mid‐to‐late embryogenesis.The observed recapitulation pattern and the developmental hourglass model may coexist.The possible evolutionary mechanisms underlying tendencies of embryonic evolution were discussed. [ABSTRACT FROM AUTHOR]

Abstract Background Embryos of taxonomically different vertebrates are thought to pass through a stage in which they resemble one another morphologically. This "vertebrate phylotypic stage" may represent the basic vertebrate body plan that was established in the common ancestor of vertebrates. However, much controversy remains about when the phylotypic stage appears, and whether it even exists. To overcome the limitations of studies based on morphological comparison, we explored a comprehensive quantitative method for defining the constrained stage using expressed sequence tag (EST) data, gene ontologies (GO), and available genomes of various animals. If strong developmental constraints occur during the phylotypic stage of vertebrate embryos, then genes conserved among vertebrates would be highly expressed at this stage. Results We established a novel method for evaluating the ancestral nature of mouse embryonic stages that does not depend on comparative morphology. The numerical "ancestor index" revealed that the mouse indeed has a highly conserved embryonic period at embryonic day 8.0–8.5, the time of appearance of the pharyngeal arch and somites. During this period, the mouse prominently expresses GO-determined developmental genes shared among vertebrates. Similar analyses revealed the existence of a bilaterian-related period, during which GO-determined developmental genes shared among bilaterians are markedly expressed at the cleavage-to-gastrulation period. The genes associated with the phylotypic stage identified by our method are essential in embryogenesis. Conclusion Our results demonstrate that the mid-embryonic stage of the mouse is indeed highly constrained, supporting the existence of the phylotypic stage. Furthermore, this candidate stage is preceded by a putative bilaterian ancestor-related period. These results not only support the developmental hourglass model, but also highlight the hierarchical aspect of embryogenesis proposed by von Baer. Identification of conserved stages and tissues by this method in various animals would be a powerful tool to examine the phylotypic stage hypothesis, and to understand which kinds of developmental events and gene sets are evolutionarily constrained and how they limit the possible variations of animal basic body plans.