Current Topics in Developmental Biology最新文献

In mammals, differentiation of germ cells is crucial for sexual reproduction, involving complex signaling pathways and environmental cues defined by the somatic cells of the gonads. This review examines the long-standing model positing that all-trans retinoic acid (ATRA) acts as a meiosis-inducing substance (MIS) in the fetal ovary by inducing expression of STRA8 in female germ cells, while CYP26B1 serves as a meiosis-preventing substance (MPS) in the fetal testis by degrading ATRA and preventing STRA8 expression in the male germ cells until postnatal development. Recent genetic studies in the mouse challenge this paradigm, revealing that meiosis initiation in female germ cells can occur independently of ATRA signaling, with key roles played by other intrinsic factors like DAZL and DMRT1, and extrinsic signals such as BMPs and vitamin C. Thus, ATRA can no longer be considered as 'the' long-searched MIS. Furthermore, evidence indicates that CYP26B1 does not prevent meiosis by degrading ATRA in the fetal testis, but acts by degrading an unidentified MIS or synthesizing an equally unknown MPS. By emphasizing the necessity of genetic loss-of-function approaches to accurately delineate the roles of signaling molecules such ATRA in vivo, this chapter calls for a reevaluation of the mechanisms instructing and preventing meiosis initiation in the fetal ovary and testis, respectively. It highlights the need for further research into the molecular identities of the signals involved in these processes.

Ovulation of a mammalian oocyte from its follicle, which occurs in response to luteinizing hormone (LH), requires complex restructuring of the ∼20 layers of surrounding somatic cells. This chapter describes the cellular architecture of preovulatory follicles, the localization of the receptors for LH, and the LH-induced changes in follicular structure, focusing on mice and other small mammals. The multiple interrelated processes that result in ovulation include breakdown of existing extracellular matrix, generation of new extracellular matrix, thinning of the follicular apex where the oocyte will be released, invagination of the follicular surface, and responses of the vascular system to support these dynamic changes. However, much remains unknown about how these events function together to release a fertilizable egg.

Double fertilization is a defining feature of flowering plants, in which two male gametes (sperm cells) fuse with two female gametes (egg and central cell) to trigger embryogenesis and endosperm development. Gamete activation before fertilization is essential for the success of fertilization, while gamete activation after fertilization is the prerequisite for embryo and endosperm development. The two phases of activation are an associated and continuous process. In this review, we focus on current understanding of gamete activation both before and after fertilization in flowering plants, summarize and discuss the detailed cellular and molecular mechanisms underlying gamete activation for fertilization or initiation of embryogenesis and endosperm development.

The zona pellucida (ZP) is a relatively thick extracellular matrix (ECM) that surrounds all mammalian eggs and plays vital roles during oogenesis, fertilization, and preimplantation development. The ZP is a semi-permeable, viscous ECM that consists of three or four glycosylated proteins, called ZP1-4, that differ from proteoglycans and proteins of somatic cell ECM. Mammalian ZP proteins are encoded by single-copy genes on different chromosomes and synthesized and secreted by growing oocytes arrested in meiosis. Secreted ZP proteins assemble in the extracellular space into long fibrils that are crosslinked polymers of ZP proteins and exhibit a structural repeat. Several regions of nascent ZP proteins, the signal-sequence, ZP domain, internal and external hydrophobic patches, transmembrane domain, and consensus furin cleavage-site regulate secretion and assembly of the proteins. The ZP domain is required for assembly of ZP fibrils, as well as for assembly of other kinds of ZP domain-containing proteins. ZP proteins adopt immunoglobulin (Ig)-like folds that resemble C- and V-type Ig-like domains, but represent new immunoglobulin-superfamily subtype structures. Interference with synthesis, processing, or secretion of ZP proteins by either gene-targeting in mice or mutations in human ZP genes can result in failure to assemble a ZP and female infertility. ZP2 and ZP3 must be present to assemble a ZP during oocyte growth and both serve as receptors for binding of free-swimming sperm to ovulated eggs. Acrosome-reacted sperm bind to ZP2 polypeptide by inner-acrosomal membrane and acrosome-intact sperm bind to ZP3 oligosaccharides by plasma membrane overlying the sperm head. Binding of acrosome-intact sperm to ZP3 induces them to undergo cellular exocytosis, the acrosome reaction. Only acrosome-reacted sperm can penetrate the ZP, bind to, and then fuse with the egg's plasma membrane to produce a zygote. Following sperm-egg fusion (fertilization) the ZP undergoes structural and functional changes (zona reaction) induced by cortical granule components (cortical reaction) deposited into the ZP. The latter include zinc and ovastacin, a metalloendoprotease that cleaves ZP2 near its amino-terminus and hardens the egg's ZP. The changes prevent penetration of bound sperm through and binding of supernumerary sperm to the ZP of fertilized eggs as part of a secondary or slow block to polyspermy. Therefore, ZP proteins act as structural proteins and sperm receptors, and help to prevent fertilization by more than one sperm. Here we review some of this information and provide details about several key features of ZP proteins, ZP matrix, and mammalian fertilization.

The vestibular apparatus of the inner ear functions to sense gravity and motion. Working together with the visual and proprioceptive systems via various muscular reflexes, it enables an organism to stabilise head position, gaze and body posture, both at rest and during movement. These functions are dependent on sensory hair cells that respond to mechanical stimulation, together with their associated non-sensory structures, including fluid-filled ducts and chambers, specialised extracellular matrices, and biomineralised crystalline deposits. The focus of this review is on the embryonic development of selected elements of the vestibular system: morphogenesis of the semicircular canal ducts, development of the ampullae and sensory cristae, and formation of the biomineralised otoliths and otoconia. Recent findings have identified new genetic players, dynamic cross-repressive gene regulatory networks, and morphogenetic mechanisms that act to shape the developing vestibular system. A final section of the review highlights approaches that link developmental genetic studies to an understanding of cell and tissue mechanics, vestibular-driven behaviour, evolution and human disease.

Gamete nuclear migration is a critical process during fertilization in flowering plants, yet its molecular mechanisms remain poorly understood. Recent studies have highlighted the essential role of cytoskeletal elements, particularly F-actin, in directing sperm nuclear migration, which differ from the microtubule-driven migration in animals. We summarize the process of sperm nuclear migration in plants and the involvement of Class XI myosin XI-G in Arabidopsis, along with the ROP8-SCAR2 pathway's ARP2/3-independent mechanism for F-actin nucleation. We also provide a comparative overview of examples from sea urchins, C. elegans, mice and yeast contrasting these mechanisms with those in plants. Finally, we outline possible future research directions related to sperm nuclear migration in plants. This review highlights the need for further exploration of pre- and post-fertilization processes, emphasizing their importance in plant cytoskeleton biology and the coordinated development of seeds.

The African clawed frog, Xenopus laevis, has long been a model organism for studying fertilization due to its large and abundant eggs that are easily manipulated and rapidly undergo embryonic development. Research on this model organism has provided significant insights into the mechanisms that ensure successful fertilization, including the prevention of polyspermy. Polyspermy, the fertilization of an egg by multiple sperm, poses a significant threat to successful embryonic development in most sexually reproducing animals. To counter this, eggs have evolved mechanisms known as polyspermy blocks, which prevent additional sperm from entering once fertilization has occurred. This review focuses on fertilization research in general, and specifically on studies of the fast block to polyspermy in X. laevis. We trace key discoveries and experimental advancements that have shaped our current understanding. Indeed, studies on X. laevis have revealed that fertilization triggers a depolarization of the egg membrane mediated by an efflux of Cl^- through the Ca²⁺-activated Cl^- channel TMEM16A, effectively preventing polyspermy. Despite these advances, several questions remain regarding the precise molecular interactions and signaling pathways involved. Continued research on X. laevis promises to uncover further details about the earliest events in embryogenesis and the voltage-dependent mechanisms of fertilization, offering broader insights into reproductive biology across species.

Congenital obstructive uropathy (COU) encompasses a heterogeneous group of anomalies arising during critical stages of fetal development, which are characterized by functional or structural obstruction of the urinary tract. This obstruction hampers normal urine flow, and the resulting urinary pressure build-up can damage the developing kidneys and bladder. COU pathogenesis is complex and its clinical outcomes are highly variable, ranging from asymptomatic ultrasonographic abnormalities to end-stage kidney disease. This review examines the developmental and genetic mechanisms underlying COU and the associated organ damage, with a focus on intrinsic, isolated forms. Although genetic studies have improved our understanding of the molecular pathways involved in urinary tract maldevelopment, most patients lack a genetic diagnosis. Hence, multiple etiologic factors appear at play, including (epi)genetic and environmental. Closing gaps in our knowledge of kidney and urinary tract development and their interdependency for normal function is essential for developing personalized care to ultimately improve patient outcomes.

All-trans retinoic acid (ATRA) signaling is essential in numerous different biological contexts. This review highlights the diverse roles of ATRA during development, function, and diseases of the pancreas. ATRA is essential to specify pancreatic progenitors from gut tube endoderm, endocrine and exocrine differentiation, and adult islet function. ATRA concentration must be carefully regulated during the derivation of islet-like cells from human pluripotent stem cells (hPSCs) to optimize the expression of key pancreatic transcription factors while mitigating adverse and unwanted cell-types in these cultures. The ATRA pathway is integral to the pancreas and here we will present selected studies from decades of research that has laid the essential groundwork for ongoing projects dedicated to unraveling the complexities of ATRA signaling in the pancreas.