Current Topics in Developmental Biology最新文献

Contrary to a common misconception that the fertilizing spermatozoon acts solely as a vehicle for paternal genome delivery to the zygote, this chapter aims to illustrate how the male gamete makes other essential contributions , including the sperm borne-oocyte activation factors, centrosome components, and components of the sperm proteome and transcriptome that help to lay the foundation for pregnancy establishment and maintenance to term, and the newborn and adult health. Our inquiry starts immediately after sperm plasma membrane fusion with its oocyte counterpart, the oolemma. Parallel to and following sperm incorporation in the egg cytoplasm, some of the sperm structures (perinuclear theca) are dissolved and spent to induce development, others (nucleus, centriole) are transformed into zygotic structures enabling it, and yet others (mitochondrial and fibrous sheath, axonemal microtubules and outer dense fibers) are recycled as to not stand in its way. Noteworthy advances in this research include the identification of several sperm-borne oocyte activating factor candidates, the role of autophagy in the post-fertilization sperm mitochondrion degradation, new insight into zygotic centrosome origins and function, and the contributions of sperm-delivered RNA cargos to early embryo development. In concluding remarks, the unresolved issues, and clinical and biotechnological implications of sperm-vectored paternal inheritance are discussed.

Egg activation is a global cellular change that, in combination with fertilization, transitions the differentiated, developmentally quiescent oocyte into a totipotent, developmentally active one-cell embryo. In C. elegans, key regulators of egg activation include egg-3, egg-4, egg-5, chs-1, and spe-11. Here we will review our current understanding of how these molecules, and others, ensure the robust activation of the egg by controlling meiosis, formation of the eggshell, and the block to polyspermy.

All-trans retinoic acid (ATRA) signaling is a major pathway regulating numerous differentiation, proliferation, and patterning processes throughout life. ATRA biosynthesis depends on the nutritional availability of vitamin A and other retinoids and carotenoids, while it is sensitive to dietary and environmental toxicants. This nutritional and environmental influence requires a robustness response that constantly fine-tunes the ATRA metabolism to maintain a context-specific, physiological range of signaling levels. The ATRA metabolic and signaling network is characterized by the existence of multiple enzymes, transcription factors, and binding proteins capable of performing the same activity. The partial spatiotemporal expression overlap of these enzymes and proteins yields different network compositions in the cells and tissues where this pathway is active. Genetic polymorphisms affecting the activity of individual network components further impact the network composition variability and the self-regulatory feedback response to ATRA fluctuations. Experiments directly challenging the robustness response uncovered a Pareto optimality in the ATRA network, such that some genetic backgrounds efficiently deal with excess ATRA but are very limited in their robustness response to reduced ATRA and vice versa. We discuss a network-focused framework to describe the robustness response and the Pareto optimality of the ATRA metabolic and signaling network.

The retina is a highly complex neural organ that captures light and converts it into electrochemical signals that are transmitted to the brain to generate vision. There are five basic types of neurons that can be further divided into many specific subtypes, and one type of glial cell, all of which are generated during development from a common progenitor cell. The process by which this diversity of neurons is generated during development has been the subject of active investigation for over 40 years, and this review attempts to summarize the key concepts that have emerged. For example, many of the transcription factors that drive the progenitor to specific neuron types have been identified. Recent single cell genomic technologies have confirmed many of the discoveries in this field, but also highlighted gaps in our knowledge, e.g., the mechanisms of neuron subtype specification. In addition, several key issues in retinal neurogenesis are still unknown and require further study. We suggest that studying animals beyond the traditional model systems may shed light on some of the unresolved questions by highlighting mechanisms that allow species specializations in vision.

Gustation, or the sense of taste, is essential for distinguishing harmful and nutritious substances, and therefore crucial for health and survival. Taste buds (TBs) located in specialized gustatory papillae on the dorsal surface of the tongue are assemblages of specialized epithelial cells called taste receptor cells (TRCs). With the help of saliva, TRCs transduce sweet, sour, salt, bitter and umami stimuli into electrochemical signals that are transmitted to the brain via gustatory sensory neurons of the VII^th and IX^th cranial ganglia. TBs in the anterior tongue are derived from embryonic ectoderm, while those in the posterior tongue arise from the endoderm. However, regardless of origin and location, all cells in adult taste buds are continually and reliably renewed, such that the sense of taste remains constant. Disruption of this regenerative process in disease or injury can lead to taste dysfunction, or dysgeusia, which negatively impacts quality of life. Decades of research into development and maintenance of adult taste epithelium have revealed molecular and cellular mechanisms underlying these processes. Here, we discuss current findings in the context of the original discoveries related to taste development and regeneration, as well as the transition from developmental to homeostatic mechanisms. Additionally, we review what is currently understood of how cancer therapies cause taste dysfunction and how the taste periphery responds to injury and inflammation. Finally, we consider future directions for the taste field and discuss several outstanding questions for further investigation.

Development is often described as following a 'genetic programme', yet perturbations to normal development, whether applied by an experimenter, the environment, or a mutation affecting development of a nearby part of the body, show developmental biology to be remarkably adaptable. This paper examines the evidence for adaptability in kidney development, focusing specifically on error-correction, self-organization, and homeorhesis (the dynamic equivalent to homeostasis: return of a perturbed system to a standard developmental trajectory, rather than a return to a fixed state that is seen in homeostasis). We present evidence for self-organization of renal tissue from randomly-aggregated progenitor cells, and also for the limitations of this self-organization and how they can be transcended by experimentally-applied symmetry-breaking cues. We provide evidence for error-correcting systems, and some evidence in the literature, generally in papers devoted to other problems, for genuine homeorhesis in aspects of kidney development. This review is not intended to be a 'last word' on any of these topics, and certainly not on the last-mentioned, for which data are very scant. It is instead intended to stimulate research in these areas, particularly homeorhesis, partly to increase understanding of natural development and partly as an aid to renal tissue engineering.

Merkel cells are epidermal mechanosensory cells that are crucial for transducing light touch sensations. The development of Merkel cells is influenced by various signaling pathways and is tightly regulated at the transcriptional and epigenetic levels. While studies have shed light on how Merkel cells develop, there is limited understanding of their maintenance in adulthood and their roles in maintaining our health. Intriguingly, emerging research on Merkel cells is slowly uncovering their functions in chronic itch, alloknesis, and potentially cancer, thereby promoting our understanding of their role in various disease states.

The mammalian inner ear contains six mechanosensory organs responsible for detecting sound, linear and angular acceleration. Each organ contains sensory hair cells that respond to mechanical stimulation and form synapses with afferent auditory and vestibular neurons. The precise arrangement of the six sensory organs and the neurons that innervate them is controlled by a variety of extracellular signals that first induce the inner ear, pattern its cardinal axes, and then fix the position of each sensory organ in space. The interplay between successive sets of signals and the transcriptional regulators that mediate their action leads to the formation of morphologically complex yet highly sensitive hearing and balance organs. This chapter will review these signals and regulators, with particular emphasis on the formation of the organ of Corti, the hearing organ of the cochlea, which exhibits one of the most finely patterned cellular arrays in vertebrates.

Hair cells (HCs) are specialized sensory receptors in auditory, vestibular, and lateral-line organs that convert mechanical stimuli into neural signals. Auditory HCs transduce sound vibrations, vestibular HCs detect head movements for balance, and lateral-line HCs in aquatic vertebrates sense water currents, providing environmental awareness. A key feature of all HCs is their directional sensitivity, determined by the graded height architecture of their hair bundle. This arrangement ensures optimal HC activation when the hair bundle is deflected towards its tallest side. Within sensory organs, HCs and their hair bundles are precisely aligned within the epithelium plane, another key feature which produces coherent responses for accurate sensory representation. HC alignment is governed by planar cell polarity (PCP) cues relayed between neighboring cells. In some epithelia, such as the mammalian auditory epithelium, HCs are uniformly oriented. In other epithelia, PCP cues can be interpreted differently, and HCs exhibit a normal or reversed orientation creating a mirror-image HC organization. Several mechanisms generate directional sensors with proper alignment. During early development, the apical cytoskeleton breaks central symmetry and produces a staircase-like hair bundle. Over time, the asymmetrical apical cytoskeleton couples with distinct PCP mechanisms and signaling molecules at cell-cell junctions, orienting HCs properly within the sensory epithelium. This chapter highlights our current understanding of the intricate polarization processes that enable HCs to function as directional sensors, providing insights into their critical role in sensory perception and spatial orientation.