Current Topics in Developmental Biology最新文献

Acute kidney injury (AKI), acute kidney disease (AKD), and chronic kidney disease (CKD) affect millions worldwide, presenting an escalating health care and economic burden, while current treatments primarily focus on slowing further kidney function loss. Treatment failure can lead to end-stage kidney disease (ESKD), which necessitates kidney replacement therapies, including dialysis-which significantly reduces quality of life-or kidney transplantation. However, limited organ availability extends waiting times to up to 10-15 years in some European countries, such as the United Kingdom and Germany. The urgent need for regenerative therapies that promote kidney recovery and potentially enable the development of de novo human kidneys places the zebrafish as a powerful model organism for these studies. Zebrafish can regenerate kidney function after AKI by forming new nephrons that integrate into the existing tubular network. Using zebrafish to investigate kidney development and injury-induced regeneration allows for the discovery of key pathways involved in renal repair and development. Importantly, adult zebrafish possess a niche of kidney progenitor cells that facilitate regeneration after injury. This chapter provides an overview of kidney development and regeneration mechanisms, highlights current experimental approaches for modeling kidney injury, and explores potential translational implications for human kidney regenerative therapies.

Mechanistic studies of renal development arguably began 70 years ago, in 1955 when Clifford Grobstein identified an inductive interaction between ureteric bud and metanephric mesenchyme. As an introduction to a special volume of Current Topics in Developmental Biology, this review looks back over the decades since Grobstein's paper to ask how well we have now answered the mechanistic questions raised in his 'pre-molecular' age, and to highlight new questions that have emerged from an increasing understanding of how kidneys develop. I consider that some old questions, such as lineage, have been answered fairly comprehensively. Some questions such as the nature of inductive signalling have become much more complicated, as a notion of 'the signal' has been replaced by hundreds, or possibly thousands, of communications that coordinate renal development. Some old questions, particularly about morphogenesis, remain open. Others, such as metabolism, were ignored for decades but are now being studied again, very profitably. New topics, such as stem cell behaviour, self-organization, epigenetics and congenital abnormalities, join work on the old ones. We have undoubtedly learned much over the last 70 years but, strangely perhaps, the number of questions still to be answered now seems much larger than it did in decades long past.

The accurate representation of sound in the central auditory pathway of mammals depends on the cochlea, the peripheral sensory organ, which is optimised to detect acoustic signals with unparalleled temporal precision. Beyond its role in converting acoustic stimuli into electrical signals, the cochlea also plays a key role in shaping the maturation of the auditory pathway during pre-hearing stages. This process is essential for creating the tonotopic maps used to identify a broad range of sound frequencies. To achieve this extraordinary task, the sensory hair cells and supporting cells of the pre-hearing cochlear sensory epithelium generate spontaneous, sensory-independent Ca²⁺ signals that propagate along the ascending auditory pathway. Here we review the current understanding of how the different Ca²⁺ signals are generated within the developing cochlea, how they interact to regulate the activation of the auditory afferent fibres, and how they ultimately contribute to the establishment of a mature auditory system pathway. Remarkably, a partial regression to an immature developmental stage occurs in the ageing cochlea, correlated with age-related hearing loss. Increasing our understanding of how the cochlear epithelium changes during all stage of life will inform future therapies for preventing and to reverse hearing loss.

The aberrant regulation of renal progenitor cells during kidney development leads to congenital kidney anomalies and dysplasia. Recently, significant progress has been made in understanding the metabolic needs of renal progenitor cells during mammalian kidney development, with evidence indicating that multiple metabolic pathways play essential roles in determining the cell fates of distinct renal progenitor populations. This review summarizes recent findings and explores the prospects of integrating this novel information into current diagnostic and treatment strategies for renal diseases. Reciprocal interactions between various embryonic kidney progenitor populations establish the foundation for normal kidney organogenesis, with the three principal kidney structures-the nephrons, the collecting duct network, and the stroma-being generated by nephron progenitor cells, ureteric bud/collecting duct progenitor cells, and interstitial progenitor cells. While energy metabolism is well recognized for its importance in organism development, physiological function regulation, and responses to environmental stimuli, research has primarily focused on nephron progenitor metabolism, highlighting its role in maintaining self-renewal. In contrast, studies on the metabolic requirements of ureteric bud/collecting duct and stromal progenitors remain limited. Given the importance of interactions between progenitor populations during kidney development, further research into the metabolic regulation of self-renewal and differentiation in ureteric bud and stromal progenitor cells will be critical.

Retinoids, particularly all-trans-retinoic acid (ATRA), play crucial roles in various physiological processes, including development, immune response, and reproduction, by regulating gene transcription through nuclear receptors. This review explores the biosynthetic pathways, homeostatic mechanisms, and the significance of retinoid-binding proteins in maintaining ATRA levels. It highlights the intricate balance required for ATRA homeostasis, emphasizing that both excess and deficiency can lead to severe developmental and health consequences. Furthermore, the associations are discussed between ATRA dysregulation and several diseases, including various genetic disorders, cancer, endometriosis, and heart failure, underscoring the role of retinoid-binding proteins like RBP1 in these conditions. The potential for gene-environment interactions in retinoid metabolism is also examined, suggesting that dietary factors may exacerbate genetic predispositions to ATRA-related pathologies. Methodological advancements in quantifying ATRA and its metabolites are reviewed, alongside the challenges inherent in studying retinoid dynamics. Future research directions are proposed to further elucidate the role of ATRA in health and disease, with the aim of identifying therapeutic targets for conditions linked to retinoid signaling dysregulation.

The glabrous skin of vertebrates is populated by cutaneous end-organ complexes, sensory corpuscles that are the sites at which the qualities of contacting objects (form, sharpness, pressure, hardness or vibration) are transduced into electrical signals. Structurally, these mechanotransducers are comprised of an axon, glial cells, and connective tissue sheaths. The axon is the peripheral prolongation of an Aβ low-threshold mechanoreceptor neuron; the glial cells are represented by non-myelinating terminal glial cells; and the connective sheaths are specializations of the endoneurium and/or perineurium. The variable arrangement of these three elements gives rise to the morphotypes of the cutaneous end-organ complexes typical of mammals: Meissner, Pacini and Ruffini corpuscles, and those of birds: the Grandry and Herbst corpuscles. In this review, an update is made on the development of the individual cellular components of cutaneous sensory corpuscles, and of the cutaneous endo-organ complexes as a whole. In general, cutaneous endo-organ complexes develop through complex multidirectional interactions between the Aβ-axons of mechanoreceptors and the terminal glial cells (both of which are neural crest derivatives) and the surrounding mesenchyme. The development of cutaneous endo-organ complexes in birds, rodents and humans, and the molecular mechanisms that regulate them are detailed.

Hearing loss and balance dysfunction are commonly caused by the loss of sensory hair cells, the cells which detect sound waves in the auditory organs and head movements in the vestibule. Replacement and regeneration of damaged hair cells occurs naturally in non-mammalian vertebrates such as birds and fish. While a small amount of hair cell regeneration occurs in the vestibular organs of mammals even at adult ages, this process only happens in the cochlea during the first days after birth and does not, in either system, result in recovery of function. Here, we review what is known about the natural capacity for hair cell regeneration in mammals, comparing auditory and vestibular organs. We also discuss strategies to induce the formation of new hair cells in the adult inner ear such as reprogramming the remaining supporting cells with genes to drive a hair cell fate or induce proliferation. Finally, we present a roadmap for what is needed to restore auditory and vestibular function and discuss the challenges that remain.

Vision is one of our most essential senses allowing us to see and interact with the world around us. It is dependent on the absorption and transduction of light by retinal photoreceptor cells. Each photoreceptor cell contains a highly-modified cilium that forms the photoreceptor outer segment (OS) and serves as an antenna for photons. The OS contains hundreds of disk membranes that form by an expansion of the ciliary plasma membrane. The disks are studded with an extremely high concentration of the visual pigment, thus maximizing their ability to capture photons of light. The OS forms during photoreceptor development but undergoes continuous renewal throughout the lifetime of the organism: new disks continue to form at the base of the OS and older disks are phagocytized from the OS tip by the adjacent retinal pigment epithelium. These anabolic and catabolic phases ensure that the OS can maintain its capacity to detect light, thus preserving our sense of vision.

Retinoic acid (RA) signaling plays multiple essential roles in development of the head and face. Animal models with mutations in genes involved in RA signaling have enabled understanding of craniofacial morphogenic processes that are regulated by the retinoid pathway. During craniofacial morphogenesis RA signaling is active in spatially restricted domains defined by the expression of genes involved in RA production and RA breakdown. The spatial distribution of RA signaling changes with progressive development, corresponding to a multiplicity of craniofacial developmental processes that are regulated by RA. One important role of RA signaling occurs in the hindbrain. There RA contributes to specification of the anterior-posterior (AP) axis of the developing CNS and to the neural crest cells (NCC) which form the bones and nerves of the face and pharyngeal region. In the optic vesicles and frontonasal process RA orchestrates development of the midface, eyes, and nasal airway. Additional roles for RA in craniofacial development include regulation of submandibular salivary gland development and maintaining patency in the sutures of the cranial vault.