Current Topics in Developmental Biology最新文献

Most animals have male and female, whereas flowering plants are hermaphrodites. Exceptionally, a small population of invertebrates, including ascidians and nematodes, has hermaphrodite in reproductive strategies. Several ascidians exhibit strict self-sterility (or self-incompatibility), similar to flowering plants. Such a self-incompatibility mechanism in ascidian has been revealed to be very similar to those of flowering plants. Here, we describe the mechanisms of ascidian fertilization shared with invertebrates and mammals, as well as with plants. In the nematode Caenorhabditis elegans, having self-fertile hermaphrodite and male, several genes responsible for fertilization are homologous to those of mammals. Thus, novel proteins responsible for fertilization will be easily disclosed by the analyses of sterile mutants. In this review, we focus on the same or similar reproductive strategies by shedding lights on the common mechanisms of fertilization, particularly in hermaphrodites.

Cell migration is a fundamental process essential for homeostasis, disease progression, and developmental biology. This review explores the mechanisms of cell migration, focusing on both single-cell and collective migration modes, and highlights their roles in early development. We examine the characteristics of amoeboid and mesenchymal migration, emphasizing their regulation and implications across various classical developmental models. By analyzing examples of single-cell migration, such as primordial germ cell migration in zebrafish and Drosophila melanogaster, and examples of collective cell migration in the lateral line of zebrafish, border cells, and testis myotubes in Drosophila, we illustrate the complexity and significance of cell-cell interactions, cell-matrix interactions, and the chemical and mechanical cues that drive migration. The review also highlights the "supracellular organization" observed in many systems where supracellular actomyosin cables are present, which allow for coordinated and cooperative movement. This cooperativity is crucial for effective positioning and function, ensuring proper tissue formation and responsive adaptation to environmental cues. This review provides insights and raises questions about the mechanisms of cell migration during development, supporting the idea that cells never migrate entirely alone. We propose that even in those cases normally described as single cell migration, some degree of collectiveness or cooperation is involved, suggesting that during development, cells always migrate in collective coordination when forming complex tissue and organ structures.

The neural crest is a highly invasive, multipotent embryonic cell population common to all vertebrates. Neural crest cells migrate all along the anteroposterior axis of the vertebrate embryos, crossing complex microenvironments during their journey and eventually halting their migration to give rise to a variety of derivatives. At cranial levels, neural crest cells originate cartilage and bone of the skull and face, cranial ganglia and glia and pigment cells. In contrast, neural crest of the trunk is unable to form ectomesenchymal tissues such as cartilage and bone, but instead contributes to the cardiac outflow tract, enteric neurons, sensory and sympathetic neurons, Schwann cells and pigment across the vertebrate trunk. Defects in neural crest formation and migration can result in an array of birth defects and childhood malignancies collectively known as neurocristopathies, and investigation of the mechanisms underlying neural crest migration has significant clinical relevance. Considerable progress has been made in recent years in our understanding of the principles underlying collective cell migration of cranial neural crest cells. However, the extracellular environment trunk neural crest traverse in vivo is radically different from that experienced by cranial neural crest cells. Here, we review collective cell migration, fate specification and current in vivo and in vitro models of trunk neural crest migration under the lens of the complex interaction of this extraordinary cell population with its complex tissue environment.

Alterations in tissue expression levels of both retinol-binding protein 2 (RBP2) and retinol-binding protein 4 (RBP4) have been associated with metabolic disease, specifically with obesity, glucose intolerance and hepatic steatosis. Our laboratories have shown that this involves novel pathways not previously considered as possible linkages between impaired retinoid metabolism and metabolic disease development. We have established both biochemically and structurally that RBP2 binds with very high affinity to very long-chain unsaturated 2-monoacylglycerols like the canonical endocannabinoid 2-arachidonoyl glycerol (2-AG) and other endocannabinoid-like substances. Binding of retinol or 2-MAGs involves the same binding pocket and 2-MAGs are able to displace retinol binding. Consequently, RBP2 is a physiologically relevant binding protein for endocannabinoids and endocannabinoid-like substances and is a nexus where the very potent retinoid and endocannabinoid signaling pathways converge. When Rbp2-null mice are challenged orally with fat, this gives rise to elevated levels in the proximal small intestine of both 2-AG and the incretin hormone glucose-dependent insulinotropic polypeptide (GIP) in the proximal small intestine. We propose that elevation of GIP concentrations upon high fat diet feeding gives rise to obesity and the other elements of metabolic disease seen in Rbp2-null mice. Unexpectedly, we observed that RBP4 is present in secretory granules of the GIP-secreting intestinal K-cells and is co-secreted with GIP in response to a stimulus that provokes GIP secretion. Moreover, RBP4 is co-secreted along with glucagon from pancreatic alpha-cells in response to a secretory stimulus. The association during the secretory process of RBP4 with potent hormones that regulate metabolism (GIP and glucagon) accounts for at least some of the metabolic disease seen upon overexpression of Rbp4.

Our sense of hearing is initiated when sound-induced vibrations deflect specialized mechanosensory projections, stereocilia, emanating from the apical surface of the inner ear hair cells. Each hair cell has dozens of stereocilia organized into rows of increasing heights, forming a "hair" bundle. This "staircase" architecture of the stereocilia bundle is common for all vertebrate hair cells and essential for normal mechanosensitivity. Yet, the molecular mechanisms underlying its formation and lifelong maintenance in non-regenerating mammalian auditory hair cells represent a fascinating but yet puzzling problem for cell biology. Recent data demonstrating that stereocilia dimensions are controlled by the ionic current through mechanosensitive channels at the tips of stereocilia may help in solving this puzzle. The current chapter describes potential molecular mechanisms of stereocilia bundle formation and maintenance, as well as the mechanisms that optimize the mechanical properties of the hair bundle for effective mechanosensation.

Advances in 'omics' technologies have uncovered new insights into photoreceptor development. Dynamic expression of and interaction among transcription factors in post-mitotic photoreceptor precursors guide cone and rod cell fate and maturation, as well as homeostasis. Together with genetic and epigenetic modifications, we are now putting together the pieces of this complex puzzle to elucidate the molecular mechanisms underlying photoreceptor differentiation. In this review, we discuss our current understanding of developmental pathways that result in the generation of cones and rods from a common pool of multipotent retinal progenitor cells in mouse and human retina. We focus on the key transcription factors and integrate the knowledge from multi-omics and the genome topology datasets to highlight the importance of both genetic and epigenetic landscapes in shaping morphological and functional identity of photoreceptors.

For mammalian spermatogenesis to proceed normally, it is essential that the population of testicular progenitor cells, A undifferentiated spermatogonia (A_undiff), undergoes differentiation during the A to A1 transition that occurs at the onset of spermatogenesis. The commitment of the A_undiff population to differentiation and leaving a quiescent, stem-like state gives rise to all the spermatozoa produced across the lifespan of an individual, and ultimately determines male fertility. The action of all-trans retinoic acid (atRA) on the A_undiff population is the determining factor that induces this change. Sertoli cells, omnipresent, nurse cells within the mammalian testis are responsible for synthesizing the atRA that prompts this change in the neonatal testicular environment. The mechanism of atRA synthesis and signaling has been robustly explored and, in this review, we have summarized what is currently known about the action of testicular atRA at the onset of spermatogenesis. We have combined this with evidence gained from prominent genetic studies that have further elucidated the function of genes critical to atRA synthesis. We have additionally described the effects of the first pulse of atRA delivered to the germ cells of the testis, which has been investigated using WIN 18,446 treatment which prevents atRA synthesis and induces spermatogenic synchrony. This method provides unparalleled resolution into cell and stage specific testicular changes, and combined with transgenic animal models, has allowed researchers to elucidate much regarding the onset of spermatogenesis.

Congenital anomalies of the kidney and urinary tract (CAKUT) represent a major health burden in humans. Phenotypes range from renal hypoplasia or renal agenesis, cystic renal dysplasia, duplicated or horseshoe kidneys to obstruction of the ureteropelvic junction, megaureters, duplicated ureters, urethral valves or bladder malformations. Over the past decade, next-generation sequencing has identified numerous causative genes; however, the genetic basis of most cases remains unexplained. It is assumed that environmental factors have a significant impact on the phenotype, but, overall, the pathogenesis has remained poorly understood. Interestingly however, CAKUT is a common phenotypic feature in two human syndromes, Kabuki and Koolen-de Vries syndrome, caused by dysfunction of genes encoding for KMT2D and KANSL1, both members of protein complexes playing an important role in histone modifications. In this chapter, we discuss current knowledge regarding epigenetic modulation in renal development and a putatively under-recognized role of epigenetics in CAKUT.

Single-cell sequencing-based techniques are revolutionizing all fields of biomedical sciences, including normal kidney development and how this is disturbed in the development of Wilms tumor. The many different techniques and the differences between them can obscure which technique is best used to answer which question. In this review we summarize the techniques currently available, discuss which have been used in kidney development or Wilms tumor context, and which techniques can or should be combined to maximize the increase in biological understanding we can get from them.

Vitamin A (all-trans-retinol; at-Rol) and its derivatives, known as retinoids, have been adopted by vertebrates to serve as visual chromophores and signaling molecules, particularly in the eye/retina. Few tissues rely on retinoids as heavily as the retina, and the study of genetically modified mouse models with deficiencies in specific retinoid-metabolizing proteins has allowed us to gain insight into the unique or redundant roles of these proteins in at-Rol uptake and storage, or their downstream roles in retinal development and function. These processes occur during embryogenesis and continue throughout life. This review delves into the role of these genes in supporting retinal function and maps the impact that genetically modified mouse models have had in studying retinoid-related genes. These models display distinct perturbations in retinoid biochemistry, physiology, and metabolic flux, mirroring human ocular diseases.