Developmental Dynamics最新文献

Maternal effects, encompassing both genetic (maternally expressed gene products) and non-genetic (maternal state) influences, are powerful determinants of offspring phenotype, yet their RNA-level mechanisms remain incompletely resolved. In parallel, epitranscriptomics, an emerging field centered on chemical modifications to RNA, has revealed new layers of gene regulation with implications for cell fate, plasticity, and response to environmental cues. In this perspective article, a conceptual link is proposed between maternal effects and epitranscriptomic mechanisms, focusing on how maternal environments may shape offspring phenotypes through RNA modifications. Evidence is examined from diverse systems, including maternal deposition of modified RNAs, environmental modulation of RNA-modifying enzymes, and early developmental windows sensitive to maternal inputs. A clear distinction is drawn between placenta-mediated pathways that reprogram trophoblast/placental epitranscriptomics and direct fetal-tissue routes that act within developing organs. Although causal demonstrations are still emerging, convergent observations indicate that maternal environments can tune the offspring epitranscriptome with lasting phenotypic consequences. To articulate this emerging connection, the concept of "maternal RNA imprinting" is proposed, the idea that offspring development is shaped by maternal cues via targeted RNA modifications. This article aims not only to synthesize emerging insights across fields but also to stimulate interdisciplinary discussion and encourage investigation into the unexplored intersections of maternal biology and RNA regulation.

Background: Mycn, a MYC gene family member, is implicated in both carcinogenesis through amplification and Feingold syndrome through its deficiency. Previous studies have indicated that increased Mycn expression enhances vascularization in human neuroblastomas, yet its precise role in vascular development remains elusive.

Results: In this study, we utilized single-cell RNA-seq and live imaging analyses to confirm that mycn is expressed during zebrafish vasculogenesis. We investigated vascular development in zebrafish using a genetically engineered mycn mutation. Our findings reveal that mycn-deficient zebrafish exhibit reduced intersegmental vessels and malformed subintestinal vessels, primarily due to decreased cell proliferation in vascular endothelial cells. Importantly, we discovered that activation of PI3K signaling significantly ameliorates these vascular abnormalities.

Conclusions: Our study establishes Mycn as a key regulator of vascular development in zebrafish, acting through the PI3K signaling pathway.

Background: During ventral body wall closure in amniotes, the skeleton and muscles such as sternum, ribs, and pectoral muscles undergo a striking positional change from the dorso-lateral to mid-ventral region. The precise process of ventral body wall closure has poorly been explored. We have presented and examined two opposing models: the invading closure model, in which musculoskeletal components infiltrate into the mid-ventral tissue, and the replacing closure model, in which the original mid-ventral tissue degenerates to be replaced by the dorso-lateral body wall.

Results: We developed a new method that enables direct cell labeling with PKH dyes in late chicken embryos. Our PKH labeling has shown that the original mid-ventral tissue, including both mesodermal and ectodermal cells, is progressively confined to the midline as the closure proceeds, contradicting the invading closure model. Moreover, the dorso-lateral tissue, including not only musculoskeletal but also non-musculoskeletal components, eventually contributes to the mid-ventral region. These results support the replacing closure model.

Conclusion: The ventral body wall closure is achieved in a replacing manner. The mid-ventral region of the early body wall is a transient structure to cover the ventral surface, which is eventually eliminated to be replaced by the dorso-lateral region that represents the future definitive body wall.

Background: Actin filament organization in cardiomyocytes critically depends on the formin Fhod3, but a role for Fhod3 in skeletal muscle development has not yet been described.

Results: We demonstrate here that in zebrafish mutated for one of two fhod3 paralog genes, fhod3a, skeletal muscle of the trunk appears normal through 2 days post-fertilization, but afterward exhibits myofibril damage, including gaps between myofibrils and myofibril fragmentation. Despite the progressive nature of the myofibril damage, fhod3a mutants differ from muscular dystrophy models in that damage is exacerbated by inhibition of muscle activity, and fhod3a mutants show no evidence of sarcolemma disruption. Rather, myofibril damage appears to coincide with growth of the contractile apparatus. We find neither the second fhod3 paralog, fhod3b, nor the related fhod1 contribute to embryonic skeletal muscle development, but fish individually mutated for fhod3a, fhod3b, or fhod1 are viable and appear grossly normal as adults. This may reflect redundancy in adults, as all three are expressed in many adult organs.

Conclusions: These results indicate a fhod3-encoded formin is dispensable for initial myofibril assembly in skeletal muscle but promotes myofibril stability during muscle fiber growth. This is the first demonstration in a vertebrate that Fhod3 contributes to skeletal muscle development.

Background: Turtles hold a unique place in vertebrate evolutionary history, making them critical assets in embryology research. Yet, they remain understudied as potential model organisms in the field. Here, to support experimental manipulations with turtle embryos, we have created a complete normal table of development for comprehensive embryonic staging of Trachemys scripta, one of the most common invasive turtle species worldwide.

Results: The development of T. scripta embryos from 0 days post-oviposition (DPO) to hatching (~60 DPO) was described from approximately 300 viable eggs collected at California State University, Northridge during the 2021-2024 nesting seasons. Thirty-one stages between oviposition and hatching were identified, and anatomical structures were cataloged using the Standard Event System (SES) chart. Morphological characteristics were imaged using bright-field microscopy and, for 4',6-diamidino-2-phenylindole-stained embryos, confocal microscopy.

Conclusion: To facilitate further research with Chelonian embryos, this staging series blends previously accepted staging practices with new details of T. scripta gastrulation, SES criteria, and a photographic annotated glossary.

Background: Echinoderms are invertebrate deuterostomes closely related to chordates and have become a tractable model for the study of the evolution of mechanisms involved in development, primordial germ cell specification, and regeneration. Sea urchins rely on inherited mechanisms for germline formation while sea stars rely instead on cell-cell inductive signaling mechanisms.

Results: Here, we present a single-cell RNA sequencing of the sea star Patiria miniata development (days 1, 2, 3, and 4 after fertilization). This resource focuses mainly on the day3 larva, but also presents an integrated dataset of the 4 days combined. We identified each cell cluster of the larva using marker genes for in situ RNA hybridization and found that, surprisingly, the primordial germ cells share many gene expression profiles with cells in the coelomic pouches, and that the ectodermal epithelium is quite heterogeneous.

Conclusion: This dataset from the sea star provides a developmental trajectory of gene expression leading to each major cell type in the larva, providing a foundation for comparative analysis with other echinoderm species in parsing out mechanisms of developmental specification, regeneration, and germ line formation.

Background: Activity of the receptor tyrosine kinase PDGFRα and the tyrosine phosphatase SHP2 is critical for vertebrate craniofacial development. SHP2 has been shown to both positively and negatively regulate PDGFR signaling through the recruitment of Grb2 and dephosphorylation of the receptor, respectively. We sought to determine the effect of SHP2 binding to PDGFRα in the facial mesenchyme via phenotypic and biochemical analyses of an allelic series of mouse embryos with combined loss of both proteins in the neural crest lineage.

Results: We demonstrated that SHP2 preferentially binds PDGFRα/α homodimers among the three PDGFR dimers. We showed that double-homozygous mutant embryos exhibit a combination, but not an improvement or worsening, of the phenotypes observed upon conditional ablation of PDGFRα or SHP2 in the neural crest lineage. We further revealed that cell death in the lateral nasal and maxillary processes underlies the upper jaw phenotypes in embryos with loss of SHP2. Finally, we showed that E10.5 Pdgfra^+/fl;Shp2^fl/fl;Wnt1-Cre^+/Tg embryos have increased phosphorylation of PDGFRα and the downstream effector Erk1/2 compared to control and double-heterozygous embryos.

Conclusions: We propose a putative model in which SHP2 binds and dephosphorylates PDGFRα while simultaneously increasing survival through an Erk1/2-independent mechanism.

Background: The lungs of squamate reptiles (lizards and snakes) are highly diverse, exhibiting single chambers, multiple chambers, transitional forms with two to three chambers, along with a suite of other anatomical features, including finger-like epithelial projections into the body cavity known as diverticulae. During embryonic development of the simple, sac-like lungs of anoles, the epithelium is pushed through the openings of a pulmonary smooth muscle mesh by the forces of luminal fluid pressure. This process of stress ball morphogenesis generates the faveolar epithelium typical of squamate lungs.

Results: Here, we compared embryonic lung development in brown anoles, leopard geckos, and veiled chameleons to determine if stress ball morphogenesis is conserved across squamates and to understand the physical processes that generate transitional-chambered lungs with diverticulae. We found that epithelial protrusion through the holes in a pulmonary smooth muscle mesh is conserved across squamates. Surprisingly, however, we found that luminal inflation is not conserved. Instead, experimental and computational evidence suggests that leopard geckos and veiled chameleons may generate their faveolae via epithelial folding downstream of epithelial proliferation. Our data also suggest that the transitional chambers and diverticulae of veiled chameleon lungs may develop via apical constriction, a process known to be crucial for airway branching in the bird lung.

Conclusions: Distinct morphogenetic mechanisms generate epithelial diversity in squamate lungs, which may underpin their species-specific physiological and ecological adaptations.