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Methods in Molecular Biology (Clifton,... 2024Ctenophores are the descendants of the earliest surviving lineage of ancestral metazoans, predating the branch leading to sponges (Ctenophore-first phylogeny). Emerging... (Review)
Review
Ctenophores are the descendants of the earliest surviving lineage of ancestral metazoans, predating the branch leading to sponges (Ctenophore-first phylogeny). Emerging genomic, ultrastructural, cellular, and systemic data indicate that virtually every aspect of ctenophore biology as well as ctenophore development are remarkably different from what is described in representatives of other 32 animal phyla. The outcome of this reconstruction is that most system-level components associated with the ctenophore organization result from convergent evolution. In other words, the ctenophore lineage independently evolved as high animal complexities with the astonishing diversity of cell types and structures as bilaterians and cnidarians. Specifically, neurons, synapses, muscles, mesoderm, through gut, sensory, and integrative systems evolved independently in Ctenophora. Rapid parallel evolution of complex traits is associated with a broad spectrum of unique ctenophore-specific molecular innovations, including alternative toolkits for making an animal. However, the systematic studies of ctenophores are in their infancy, and deciphering their remarkable morphological and functional diversity is one of the hot topics in biological research, with many anticipated surprises.
Topics: Ctenophora; Animals; Phylogeny; Biological Evolution
PubMed: 38668961
DOI: 10.1007/978-1-0716-3642-8_1 -
BioRxiv : the Preprint Server For... Feb 2024To investigate the co-development of vasculature, mesenchyme, and epithelium crucial for organogenesis and the acquisition of organ-specific characteristics, we...
UNLABELLED
To investigate the co-development of vasculature, mesenchyme, and epithelium crucial for organogenesis and the acquisition of organ-specific characteristics, we constructed a human pluripotent stem cell-derived organoid system comprising lung or intestinal epithelium surrounded by organotypic mesenchyme and vasculature. We demonstrated the pivotal role of co-differentiating mesoderm and endoderm via precise BMP regulation in generating multilineage organoids and gut tube patterning. Single-cell RNA-seq analysis revealed organ specificity in endothelium and mesenchyme, and uncovered key ligands driving endothelial specification in the lung (e.g., WNT2B and Semaphorins) or intestine (e.g., GDF15). Upon transplantation under the kidney capsule in mice, these organoids further matured and developed perfusable human-specific sub-epithelial capillaries. Additionally, our model recapitulated the abnormal endothelial-epithelial crosstalk in patients with deletion or mutations. Multilineage organoids provide a unique platform to study developmental cues guiding endothelial and mesenchymal cell fate determination, and investigate intricate cell-cell communications in human organogenesis and disease.
HIGHLIGHTS
BMP signaling fine-tunes the co-differentiation of mesoderm and endoderm.The cellular composition in multilineage organoids resembles that of human fetal organs.Mesenchyme and endothelium co-developed within the organoids adopt organ-specific characteristics.Multilineage organoids recapitulate abnormal endothelial-epithelial crosstalk in FOXF1-associated disorders.
PubMed: 38370768
DOI: 10.1101/2024.02.06.577460 -
Hearing Research Oct 2023Pericytes are specialized mural cells surrounding endothelial cells in microvascular beds. They play a role in vascular development, blood flow regulation, maintenance... (Review)
Review
Pericytes are specialized mural cells surrounding endothelial cells in microvascular beds. They play a role in vascular development, blood flow regulation, maintenance of blood-tissue barrier integrity, and control of angiogenesis, tissue fibrosis, and wound healing. In recent decades, understanding of the critical role played by pericytes in retina, brain, lung, and kidney has seen significant progress. The cochlea contains a large population of pericytes. However, the role of cochlear pericytes in auditory pathophysiology is, by contrast, largely unknown. The present review discusses recent progress in identifying cochlear pericytes, mapping their distribution, and defining their role in regulating blood flow, controlling the blood-labyrinth barrier (BLB) and angiogenesis, and involvement in different types of hearing loss.
Topics: Humans; Pericytes; Endothelial Cells; Hearing Loss; Deafness; Cochlea
PubMed: 37651921
DOI: 10.1016/j.heares.2023.108877 -
Nature Feb 2024The house mouse (Mus musculus) is an exceptional model system, combining genetic tractability with close evolutionary affinity to humans. Mouse gestation lasts only 3...
The house mouse (Mus musculus) is an exceptional model system, combining genetic tractability with close evolutionary affinity to humans. Mouse gestation lasts only 3 weeks, during which the genome orchestrates the astonishing transformation of a single-cell zygote into a free-living pup composed of more than 500 million cells. Here, to establish a global framework for exploring mammalian development, we applied optimized single-cell combinatorial indexing to profile the transcriptional states of 12.4 million nuclei from 83 embryos, precisely staged at 2- to 6-hour intervals spanning late gastrulation (embryonic day 8) to birth (postnatal day 0). From these data, we annotate hundreds of cell types and explore the ontogenesis of the posterior embryo during somitogenesis and of kidney, mesenchyme, retina and early neurons. We leverage the temporal resolution and sampling depth of these whole-embryo snapshots, together with published data from earlier timepoints, to construct a rooted tree of cell-type relationships that spans the entirety of prenatal development, from zygote to birth. Throughout this tree, we systematically nominate genes encoding transcription factors and other proteins as candidate drivers of the in vivo differentiation of hundreds of cell types. Remarkably, the most marked temporal shifts in cell states are observed within one hour of birth and presumably underlie the massive physiological adaptations that must accompany the successful transition of a mammalian fetus to life outside the womb.
Topics: Animals; Female; Mice; Pregnancy; Animals, Newborn; Cell Differentiation; Embryo, Mammalian; Embryonic Development; Gastrula; Gastrulation; Kidney; Mesoderm; Neurons; Retina; Single-Cell Analysis; Somites; Time Factors; Time-Lapse Imaging; Transcription Factors; Transcription, Genetic; Organ Specificity
PubMed: 38355799
DOI: 10.1038/s41586-024-07069-w -
Current Topics in Developmental Biology 2024The Segmentation Clock is a tissue-level patterning system that enables the segmentation of the vertebral column precursors into transient multicellular blocks called... (Review)
Review
The Segmentation Clock is a tissue-level patterning system that enables the segmentation of the vertebral column precursors into transient multicellular blocks called somites. This patterning system comprises a set of elements that are essential for correct segmentation. Under the so-called "Clock and Wavefront" model, the system consists of two elements, a genetic oscillator that manifests itself as traveling waves of gene expression, and a regressing wavefront that transforms the temporally periodic signal encoded in the oscillations into a permanent spatially periodic pattern of somite boundaries. Over the last twenty years, every new discovery about the Segmentation Clock has been tightly linked to the nomenclature of the "Clock and Wavefront" model. This constrained allocation of discoveries into these two elements has generated long-standing debates in the field as what defines molecularly the wavefront and how and where the interaction between the two elements establishes the future somite boundaries. In this review, we propose an expansion of the "Clock and Wavefront" model into three elements, "Clock", "Wavefront" and signaling gradients. We first provide a detailed description of the components and regulatory mechanisms of each element, and we then examine how the spatiotemporal integration of the three elements leads to the establishment of the presumptive somite boundaries. To be as exhaustive as possible, we focus on the Segmentation Clock in zebrafish. Furthermore, we show how this three-element expansion of the model provides a better understanding of the somite formation process and we emphasize where our current understanding of this patterning system remains obscure.
Topics: Animals; Body Patterning; Gene Expression Regulation, Developmental; Somites; Mesoderm; Zebrafish; Signal Transduction; Biological Clocks
PubMed: 38729682
DOI: 10.1016/bs.ctdb.2023.11.001 -
Differentiation; Research in Biological... 2023Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial disease that is characterized by increased cellular proliferation and differentiation together with... (Review)
Review
Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial disease that is characterized by increased cellular proliferation and differentiation together with excessive extracellular matrix (ECM) deposition leading to buildup of scar tissue (fibrosis) and remodeling in the lungs. The activated and differentiated (myo)fibroblasts are one of the main sources of tissue remodeling in IPF and a crucial mechanism known to contribute to this feature is an aberrant crosstalk between pulmonary fibroblasts and the abnormal or injured pulmonary epithelium. This epithelial-fibroblast interaction mimics the temporal, spatial and cell-type specific crosstalk between the endoderm and mesoderm in the so-called epithelial-mesenchymal trophic unit (EMTU) during lung development that is proposed to be activated in healthy lung repair and dysregulated in various lung diseases including IPF. To study the dysregulated lung EMTU in IPF, various complex in vitro models have been established. Hence, in this review, we will provide a summary of studies that have used complex (3-dimensional) in vitro co-culture, and organoid models to assess how abnormal epithelial-fibroblast interactions in lung EMTU contribute to crucial features of the IPF including defective cellular differentiation, proliferation and migration as well as increased ECM deposition.
Topics: Humans; Coculture Techniques; Idiopathic Pulmonary Fibrosis; Lung; Fibroblasts; Fibrosis
PubMed: 37738701
DOI: 10.1016/j.diff.2023.09.001 -
Pharmacology & Therapeutics Sep 2023Chronic and neuropathic pain are a widespread burden. Incomplete understanding of underlying pathomechanisms is one crucial factor for insufficient treatment. Recently,... (Review)
Review
Chronic and neuropathic pain are a widespread burden. Incomplete understanding of underlying pathomechanisms is one crucial factor for insufficient treatment. Recently, impairment of the blood nerve barrier (BNB) has emerged as one key aspect of pain initiation and maintenance. In this narrative review, we discuss several mechanisms and putative targets for novel treatment strategies. Cells such as pericytes, local mediators like netrin-1 and specialized proresolving mediators (SPMs), will be covered as well as circulating factors including the hormones cortisol and oestrogen and microRNAs. They are crucial in either the BNB or similar barriers and associated with pain. While clinical studies are still scarce, these findings might provide valuable insight into mechanisms and nurture development of therapeutic approaches.
Topics: Humans; Blood-Nerve Barrier; Neuralgia; Pericytes; MicroRNAs
PubMed: 37390969
DOI: 10.1016/j.pharmthera.2023.108484 -
Developmental Cell Sep 2023Mammalian specification of mesoderm and definitive endoderm (DE) is instructed by the two related Tbx transcription factors (TFs) Eomesodermin (Eomes) and Brachyury...
Mammalian specification of mesoderm and definitive endoderm (DE) is instructed by the two related Tbx transcription factors (TFs) Eomesodermin (Eomes) and Brachyury sharing partially redundant functions. Gross differences in mutant embryonic phenotypes suggest specific functions of each TF. To date, the molecular details of separated lineage-specific gene regulation by Eomes and Brachyury remain poorly understood. Here, we combine mouse embryonic and stem-cell-based analyses to delineate the non-overlapping, lineage-specific transcriptional activities. On a genome-wide scale, binding of both TFs overlaps at promoters of target genes but shows specificity for distal enhancer regions that is conferred by differences in Tbx DNA-binding motifs. The unique binding to enhancer sites instructs the specification of anterior mesoderm (AM) and DE by Eomes and caudal mesoderm by Brachyury. Remarkably, EOMES antagonizes BRACHYURY gene regulatory functions in coexpressing cells during early gastrulation to ensure the proper sequence of early AM and DE lineage specification followed by posterior mesoderm derivatives.
Topics: Mice; Animals; Gastrulation; T-Box Domain Proteins; Mesoderm; Fetal Proteins; Gene Expression Regulation, Developmental; Mammals
PubMed: 37633271
DOI: 10.1016/j.devcel.2023.07.023 -
Cells & Development Feb 2024The discovery of the Spemann-Mangold organizer strongly influenced subsequent research on embryonic induction, with research aiming to elucidate the molecular...
The discovery of the Spemann-Mangold organizer strongly influenced subsequent research on embryonic induction, with research aiming to elucidate the molecular characteristics of organizer activity being currently underway. Herein, we review the history of research on embryonic induction, and describe how the mechanisms of induction phenomena and developmental processes have been investigated. Classical experiments investigating the differentiation capacity and inductive activity of various embryonic regions were conducted by many researchers, and important theories of region-specific induction and the concept for chain of induction were proposed. The transition from experimental embryology to developmental biology has enabled us to understand the mechanisms of embryonic induction at the molecular level. Consequently, many inducing substances and molecules such as transcriptional factors and peptide growth factors involved in the organizer formation were identified. One of peptide growth factors, activin, acts as a mesoderm- and endoderm-inducing substance. Activin induces several tissues and organs from the undifferentiated cell mass of amphibian embryos in a concentration-dependent manner. We review the extent to which we can control in vitro organogenesis from undifferentiated cells, and discuss the application to stem cell-based regenerative medicine based on insights gained from animal experiments, such as in amphibians.
PubMed: 38295873
DOI: 10.1016/j.cdev.2024.203903