Cells & Development最新文献

Induction of the neural ectoderm and the patterning of embryonic brain are the requisite organizing activity for head formation. Studies of loss-of-function mouse mutants that displayed a head truncation phenotype pointed to a key functional role of the anterior mesendoderm in anterior neural patterning. In this overview, we highlight the learning of the molecular attributes underpinning the formation of the anterior mesendoderm, the acquisition of ectoderm competence in the epiblast and the patterning of the embryonic brain during gastrulation and neurulation.

Throughout embryonic development, cells respond to a diverse set of signals and forces, making individual or collective decisions that drive the formation of specialized tissues. The development of these structures is tightly regulated in space and time. In recent years, the possibility that neighboring tissues influence one another's morphogenesis has been explored, as some of them develop simultaneously. We study this issue by reviewing the interactions between Drosophila epidermal and tracheal tissues in early and late stages of embryogenesis. Early in development, the epidermis emerges from the ectodermal layer. During its differentiation, epidermal cells produce morphogen gradients that influence the fundamental organization of the embryo. In this work, we analyze how molecules produced by the epidermis guide tracheal system development. Since both tissues emerge from the same germ layer and lie in close proximity all along their development, they are an excellent model for studying induction processes and tissue interactions.

fos genes, transcription factors with a common basic region and leucine zipper domains binding to a consensus DNA sequence (TGA{}TCA), are evolutionarily conserved in eukaryotes. Homologs can be found in many different species from yeast to vertebrates. In yeast, the homologous GCN4 gene is required to mediate "emergency" situations like nutrient deprivation and the unfolded protein response. The C. elegans homolog fos-1 is required for reproduction and vulval development, as well as in adult homeostasis. In Drosophila melanogaster, there is also a sole fos homolog: the gene kayak, with five isoforms. The kayak locus has been studied in detail. It was originally described as embryonic lethal with a "dorsal open" phenotype. Since then, kayak has been shown to be required for oocyte maturation and as a source for piRNA; for early dorsoventral specification, macrophage function, dorsal closure, endoderm differentiation, and finally during metamorphosis in wing and eye-antennal development. In mammals there are multiple fos loci, each one with alternative splicing giving rise to multiple isoforms. Overall, mammalian fos genes are required for bone, cartilage and tooth formation, and in some instances for placental angiogenesis and retinal function. We review here mainly what is known about fos function in invertebrate model systems, especially during embryogenesis. We propose that fos genes, evolutionarily conserved transcription factors, evolved early during eukaryotic development, and from its inception as part of an environmental stress response machinery, were co-opted several times during development to regulate processes that may require similar cellular responses.

Embryonic development is a complex self-organizing process orchestrated by a series of regulatory events at the molecular and cellular levels, resulting in the formation of a fully functional organism. This review focuses on activin protein as a mesoderm-inducing factor and the self-organizing properties it confers. Activin has been detected in both unfertilized eggs and embryos, suggesting its involvement in early developmental processes. To explore its effects, animal cap cells-pluripotent cells from the animal pole of amphibian blastula-stage embryos-were treated with varying concentrations of activin. The results showed that activin induced mesodermal tissues, including blood, muscle, and notochord, in a dose-dependent manner. Co-treatment with activin and retinoic acid further promoted the development of kidney and pancreatic tissues, while activin alone stimulated the formation of beating cardiac tissue. In subsequent experiments, high concentrations of activin conferred an organizer-like activity on animal cap cells. The pretreatment duration affected outcomes: longer exposure induced anterior structures, such as eyes, while shorter exposure resulted in posterior structures, like tails. These findings reflect moderate self-assembly, where cells become increasingly organized. In another experiment, activin was used to create an artificial gradient. Explants cultured on this gradient developed into embryoids with well-defined anteroposterior, dorsoventral, and left-right axes, exemplifying higher-order self-organization. These results demonstrate that controlled activin gradients can drive the formation of nearly complete tadpole-like larvae, effectively recapitulating the processes of early embryogenesis. This system offers valuable insights into the mechanisms underlying axis formation and organogenesis, providing a promising platform for future research in developmental biology.

Collective cell migration is a fundamental process underlying various biological phenomena, including embryonic development and cancer cell invasion. The cohesive yet flexible movement of cell collectives largely depends on the coordinated regulation of cell-cell and cell-substrate adhesions. In this review, we summarize the regulation of key cell-cell junction components, such as cadherins and zonula occludens proteins during collective cell migration, with a particular focus on the recently discovered multifaceted roles of ZO-1 in both cell-cell and cell-substrate interactions.

The maternal-fetal interface has long been considered as a frontier for an evolutionary arms race due to the close juxtaposition of genetically distinct tissues. In hemochorial species with deep placental invasion, including in humans, maternal stroma prepares its defenses against deep trophoblast invasion by decidualization, a differentiation process characterized by increased stromal cell matrix production, and contractile force generation. Decidualization has evolved from an ancestral wound healing response of fibroblast activation by the endometrial stroma. On the placental side, a new trophoblast cell type in great apes has recently evolved, called extravillous trophoblast (EVT), with an exceptionally high invasive capability. Using HTR8, and differentiated EVTs from trophectodermal stem cells, we show that EVTs partly counter decidual myofibroblast activation derived defenses. This reversal in decidual defenses is achieved by secreted antagonists of Transforming Growth Factor β/Bone morphogenic pathway, specifically Emilin-1 and Gremlin-1. Emilin-1 and Gremlin-1 reverse TGFβ activation in decidual cells, reducing high collagen production, and expression of genes associated with myofibroblast transformation. We also show that these secreted TGFβ antagonists can functionally reverse acquired decidual resistance to trophoblast invasion. As our work highlights new mechanisms evolved by trophoblasts to regulate stromal invasibility, it has broader implications in other invasive processes, including wound healing, and cancer metastasis.

Butterfly wing eyespots are developmentally determined at the early pupal stage, when prospective eyespot focal cells underneath the pupal cuticle focal spot function as eyespot organizers in the pupal wing tissue. Here, we performed light microscopy and transmission electron microscopy (TEM) to describe cellular structures of pupal wing tissue with an eyespot organizer immediately after pupation using the Blue Pansy butterfly Junonia orithya. The pupal forewing dorsal epidermis was a pseudostratified monolayer of vertically elongated epidermal cells. The apical portion of the cells adhered laterally to one another, but their medial and basal portions were thinner than the apical portion and were tilted to enclose cells at the center, forming a cellular cluster. The cellular cluster at the organizer was relatively large laterally and vertically. The apical portion of the cells and its corresponding cuticle at the organizer were thicker than those in the surroundings. The innermost cuticle layer was being synthesized, indicating high cuticle synthesis and secretion activity of the cells. At the medial and basal portions of the dorsal epidermis, there were many intracellular and extracellular vacuole-like globules, most likely containing extracellular matrix molecules. Some of the basal processes from epidermal cells extended to form protrusions of the basement membrane, which was often attended by hemocytes. These results suggest that the butterfly eyespot organizer is composed of a single or a few cellular clusters that secrete more cuticle than surrounding clusters, supporting the pupal cuticle hypothesis that cuticle formation is critical for eyespot color pattern determination in butterflies.

The temporal control of mitotic exit of individual Schwann cells (SCs) is essential for radial sorting and peripheral myelination. However, it remains unknown when, during their multiple rounds of division, SCs initiate myelin signaling in vivo. By manipulating SC division during development, we report that when SCs skip their division during migration, but not during radial sorting, they fail to myelinate peripheral axons. This coincides with a sharp decrease in Laminin expression within the posterior lateral line nerve. Interestingly, elevating cAMP levels or forcing Laminin 2 expression within individual SCs restore their ability to myelinate, despite missing mitosis during migration. Our results demonstrate a limited time window during which migrating SCs initiate Laminin expression to gradually activate the Laminin/Gpr126/cAMP signaling required for radial sorting and myelination at later stages in vivo.

2024 not only marked the 100th anniversary of the discovery of the organizer by Hilde Pröscholdt-Mangold and Hans Spemann, but also the 40th anniversary of the discovery of the homeobox, a DNA region encoding a DNA binding peptide present in several transcription factors of critical importance for the gastrulating embryo. In particular, this sequence is found in the 39 members of the amniote Hox gene family, a series of genes activated in mid-gastrulation and involved in organizing morphologies along the extending anterior to posterior (AP) body axis. Over the past 30 years, the study of their coordinated regulation in various contexts has progressively revealed their surprising regulatory strategies, based on mechanisms acting in-cis, which can translate a linear distribution of series of genes along the chromatin fiber into the proper sequences of morphologies observed along our various body axes. The first regulatory layer is controlled by the Hox timer, a mechanism implementing a time-sequenced activation of these genes following their chromosomal order. Here, we discuss various aspects of this mechanism, emphasizing some of its singularities.

The mammalian heart contains cardiac stem cells throughout life, but it has not been possible to harness or stimulate these cells to repair damaged myocardium in vivo. Assuming physiological relevance of these cells, which have evolved and have been maintained throughout mammalian evolution, we hypothesize that cardiac stem cells may contribute to cardiomyogenesis in an unorthodox manner. Since the intermediate filament protein desmin and the matricellular Secreted Protein Acidic and Rich in Cysteine (SPARC) promote cardiomyogenic differentiation during embryogenesis in a cell-autonomous and paracrine manner, respectively, we focus on their genes and employ mouse embryonic and cardiac stem cell lines as in vitro models to ask whether desmin and SPARC cooperatively influence cardiomyogenesis in cardiac stem and progenitor cells. We show that desmin also promotes cardiomyogenesis in a non-cell autonomous manner by increasing the expression and secretion of SPARC in differentiating embryonic stem cells. SPARC is also secreted by cardiac stem cells where it promotes cardiomyogenesis in an autocrine and concentration-dependent manner by upregulating the expression of myocardial transcription factors and its elicitor desmin. Desmin and SPARC interact genetically, forming a positive feedback loop and secreted autocrine and paracrine SPARC negatively affects sparc mRNA expression. Paracrine SPARC rescues cardiomyogenic desmin-haploinsufficiency in cardiac stem cells in a glycosylation-dependent manner, increases desmin expression, the phosphorylation of Smad2 and induces the expression of gata4, nkx2.5 and mef2C. Demonstration that desmin-induced autocrine secretion of SPARC in cardiac stem cells promotes cardiomyogenesis raises the possibility that a physiological function of cardiac stem cells in the adult and aging heart may be the gland-like secretion of factors such as SPARC that modulate age-related and adverse environmental influences and thereby contribute to cardiac homeostasis throughout life.