International Journal of Developmental Biology最新文献

Prenatal alcohol exposure (PAE) provokes lifelong CNS dysfunction, including an increased susceptibility to seizure disorders. We investigated hippocampal excitability in vitro in the offspring of dams exposed to a mild ethanol concentration throughout pregnancy (ethanol 15%v/v in drinking water). Hippocampal slices were prepared from the offspring at a young (Y, 21-30 postnatal days, PND) or adult (A, 60 PND) age, with controls from same age normal rats (N). Synchronous spontaneous interictal-type epileptiform discharges (IEDs) were induced by bathing the slices in Mg²⁺-free ACSF or in 4-Aminopyridine (4-AP, 50µΜ) and were recorded from CA1 pyramidal layer of temporal (T) and septal slices (S). Hippocampal slices readily generated IEDs following NMDA receptor activation or K⁺ conductance block, with frequency and duration depending on location (septal or temporal), age, the activating mechanism, and prior conditioning (N or PAE). From the two media, 4-AP induced higher frequency (always), shorter duration (mostly) IEDs compared to Mg ²⁺-free ACSF. Temporal IED frequency increased with age, whereas septal was stable, indicating an earlier maturation of the latter part. The hippocampal "T to S" (high to low) excitability gradient appeared at/later than the end of the first postnatal month and mostly concerned discharge frequency. Discharge duration generally decreased with maturation but appeared to depend on many factors, including conditioning. Prenatal alcohol exposure differentiated the control of synchronous discharges by NMDA receptors and K⁺ conductances, and their developmental evolution, thus suggesting potential mechanisms for aberrant hippocampal neuronal network function.

Although histone methyltransferases are implicated in many key developmental processes, the contribution of individual chromatin modifiers in dental tissues is not well understood. Using single-cell RNA sequencing, we examined the expression profiles of the disruptor of telomeric silencing 1-like (Dot1L) gene in the postnatal day 5 mouse molar dental pulp. Dot1L is the only known enzyme that methylates histone 3 on lysine 79, a modification associated with gene expression. Our research revealed 15 distinct clusters representing different populations of mesenchymal stromal cells (MSCs), immune cells, pericytes, ameloblasts and endothelial cells. We documented heterogeneity in gene expression across different subpopulations of MSCs, a good indicator that these stromal progenitors undergo different phases of osteogenic differentiation. Interestingly, although Dot1L was broadly expressed across all cell clusters within the molar dental pulp, our analyses indicated specific enrichment of Dot1L within two clusters of MSCs, as well as cell clusters characterized as ameloblasts and endothelial cells. Moreover, we detected Dot1L co-expression with protein interactors involved in epigenetic activation such as Setd2, Sirt1, Brd4, Isw1, Bptf and Suv39h1. In addition, Dot1L was co-expressed with Eed2, Cbx3 and Dnmt1, which encode epigenetic factors associated with gene silencing and heterochromatin formation. Dot1l was co-expressed with downstream targets of the insulin growth factor and WNT signaling pathways, as well as genes involved in cell cycle progression. Collectively, our results suggest that Dot1L may play key roles in orchestrating lineage-specific gene expression during MSC differentiation.

Abnormally high concentrations of all-trans retinoic acid (atRA) induce cleft palate, which is accompanied by abnormal migration and proliferation of mouse embryonic palatal mesenchyme (MEPM) cells. Hormone-sensitive lipase (HSL) is involved in many embryonic development processes. The current study was designed to elucidate the mechanism of HSL in cleft palate induced by atRA. To establish a cleft palate model in Kunming mice, pregnant mice were administered atRA (70 mg/kg) by gavage at embryonic Day 10.5 (E10.5). Embryonic palates were obtained through the dissection of pregnant mice at E15.5. Hematoxylin and eosin (H&E) staining was used to evaluate growth changes in the palatal shelves. The levels of HSL in MEPM cells were detected by immunohistochemistry, quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting. RNAi was applied to construct vectors expressing HSL small interference RNAs (siRNAs). The vectors were transfected into MEPM cells. Cell proliferation and migration were evaluated by the cell counting kit-8 (CCK-8) assay and wound healing assay, respectively. The palatal shelves in the atRA group had separated at E15.5 without fusing. In MEPM cells, the expression of HSL was reversed after atRA treatment, which caused cleft palate in vivo. In the atRA group, the proliferation of HSL siRNA-transfected cells was remarkably promoted, and the migration rate significantly increased in the HSL siRNA-transfected MEPM cells. These results suggested that HSL may be involved in cleft palate induced by atRA and that atRA enhances HSL levels to inhibit embryonic palate growth.

Brain aging is associated with alterations in the behavioral capacity to process information, due to mechanisms that are still largely unclear. Short-term neuronal activity dynamics are basic properties of local brain networks profoundly involved in neural information processing. In this study, we investigated the properties of short-term changes in excitatory synaptic transmission and neuronal excitation in the CA1 field of dorsal and ventral hippocampal slices from young adult and old rats. We found that short-term synaptic plasticity (i.e. short-term dynamics of input to CA1 circuit) does not significantly differ between young and old dorsal or ventral hippocampus. However, short-term dynamics of hippocampal output differ markedly between young and old rats. Notably, age-dependent alterations in short-term neuronal dynamics were detected mainly in the dorsal hippocampus. Thus, the dorsal hippocampus of young rats can detect and facilitate transmission of 1-30 Hz input and depress transmission of higher-frequency input. In contrast, the old dorsal hippocampus appears unable to transmit information in a frequency-dependent discriminatory manner. Furthermore, the amplification of steady-state output at frequencies < 40 Hz is considerably lower in the old than the young dorsal hippocampus. The old ventral hippocampus did not show major alterations in short-term processing of neural information, though under conditions of intense afferent activation, neuronal output of the ventral hippocampus is depressed at steady-state more in old than in young rats. These results suggest that aging is accompanied by alterations in neural information processing mainly in the dorsal hippocampus, which displays a narrower dynamic range of frequency-dependent transient changes in neuronal activity in old compared with young adult rats. These alterations in short-term dynamics may relate to deficits in processing ongoing activity seen in old individuals.

This review is an update with regard to the efforts to develop liposomal carriers for growth factor delivery. It is well known that growth factors have the potential to enhance/accelerate tissue regeneration; however, their poor stability, which results in rapid loss of their activity, together with their rapid clearance from defected tissues (when applied as free molecules) is a serious drawback for their use; their highly hydrophilic nature and low capability to permeate through biological barriers (cell membranes) are additional factors that limit their applicability. In recent years, the advantages of liposomal drug delivery systems have motivated efforts to deliver growth factors (GFs) in liposomal form. Herein, after briefly introducing the basic structural characteristics of liposome types and their advantages when used as drug carriers, as well as the basic problems encountered when GFs are applied for tissue regeneration, we focus on recent reports on the development and potential regenerative effects of liposomal GFs, towards defects of various tissues. The methodologies used for incorporation, attachment or immobilization of liposomal GFs in order to sustain their retention at the defected tissues are also highlighted.

The superiority of the mammalian central nervous system (CNS) compared with other vertebrates does not involve an advanced capacity for regeneration, and any insult results in irreversible functional loss. Spinal cord injury (SCI) is one example of CNS trauma affecting thousands of individuals, mostly young, each year. Despite enormous progress in our comprehension of the molecular and cellular mechanisms underlying the pathophysiology after SCI, also providing targets for therapeutic interventions, no efficient therapy exists as yet, emphasizing the need for further research. A breadth of studies have demonstrated that, after SCI, principles of development come into play either to promote or to prohibit spontaneous regeneration, and their appropriate manipulation has the potential to contribute towards functional recovery. In this overview, some of the most recent and important studies are discussed.These offer explicitly novel input from the field of development to the field of CNS repair regarding the modification of the inhibitory environment of the injured spinal cord - mainly referring to the glial scar - the activation of endogenous cell populations such as ependymal stem cells and oligodendrocyte precursor cells, and the developmental transcriptional program that is transiently activated in neurons after injury. Furthermore, current advances in stem cell technology are highlighted in terms of refinement and precise design of the appropriate stem cell population to be transplanted, not only for cell replacement but also for modulation of the host environment. As single-dimension applications have not yet proved clinically successful, it is suggested that combinatorial strategies tackling more than one target might be more effective.

The promyelocytic leukemia protein (PML) is the core organizer of cognate nuclear bodies (PML-NBs). Through physical interaction or modification of diverse protein clients, PML-NBs regulate a multitude of - often antithetical- biological processes such as antiviral and stress response, inhibition of cell proliferation and autophagy, and promotion of apoptosis or senescence. Although PML was originally recognized as a tumor-suppressive factor, more recent studies have revealed a "double-faced" agent role for PML. Indeed, PML displayed tumor cell pro-survival and pro-migratory functions via inhibition of migration suppressing molecules or promotion of transforming growth factor beta (TGF-β) mediated Epithelial-Mesenchymal Transition (EMT) that may promote cancer cell dissemination. In this line, PML was found to correlate with poor patient prognosis in distinct tumor contexts. Furthermore, in the last decade, a number of publications have implicated PML in the physiology of normal or cancer stem cells (CSCs). Promyelocytic leukemia protein activates fatty acid oxidation (FAO), a metabolic mechanism required for the asymmetric divisions and maintenance of hematopoietic stem cells (HSCs). In embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), PML is required for maintenance of the naïve and acquisition of the induced pluripotency state, respectively. Correspondingly, PML ablation causes significant morphological gene expression and lineage choice changes. In this review, we focus on the mechanisms orchestrated by PML and PML-NBs in cancer and healthy stem cells, from cell physiology to the regulation of chromatin dynamics.

Although neuron birth and death are two contradictory processes, they serve the same purpose of the formation of the brain. They coexist during brain development, when cytoarchitecture and synaptic contacts are progressively established. It is the highly programmed interplay between these two processes that results in the making of a mature, complex-wired, functional brain. Neurogenesis is the process that begins with the birth of naïve new neurons, which are gradually specified to their prospective cell fate, translocate through migratory streams to the brain area they are destined for, and terminally differentiate into mature neurons that integrate into neuronal networks with sophisticated functions. This is an ongoing process until adulthood, when it mediates brain neuroplasticity. Neuron death is the process through which the fine sculpting and modeling of the brain is achieved. It serves to adjust final neuron numbers, exerting quality control over neurons that birth has generated or overproduced. It additionally corrects early wiring and performs systems matching by negatively selecting neurons that fail to gain neurotransmitter-mediated neuronal activity or receive neurotrophic support for maintenance and function. It is also a means by which organizing centers and transient structures are removed early in morphogenesis. Both processes are evolutionary conserved, genetically programmed and orchestrated by the same signaling factors regulating the cell cycle, neuronal activity/neurotransmitter action and neurotrophic support. This review summarizes and highlights recent knowledge with regard to birth and death of neurons, the two mutually dependent contributors to the formation of the highly evolved mammalian brain.

The secreted growth factor pleiotrophin (PTN) is expressed in all species and is evolutionarily highly conserved, suggesting that it plays a significant role in the regulation of important processes. The observation that it is highly expressed at early stages during development and in embryonic progenitor cells highlights a potentially important contribution to development. There is ample evidence of the role of PTN in the development of the nervous system and hematopoiesis, some, albeit inconclusive, evidence of its role in the skeletomuscular system, and limited evidence of its role in the development of other organs. Studies on its role in the cardiovascular system and angiogenesis suggest that PTN has a significant regulatory effect by acting on endothelial cells, while its role in the functions of smooth or cardiac muscle cells has not been studied. This review highlights what is known to date regarding the role of PTN in the development of various organs and in angiogenesis. Wherever possible, evidence on the crosstalk between the receptors that mediate PTN's functions is also quoted, highlighting the complex regulatory pathways that affect development and angiogenesis.

Myocardial regeneration is identified as a concept at histological level. The core content is to increase the number of cardiomyocytes (CMs), so as to maintain the steady state of CMs under pathological or physiological conditions and ensure the normal cardiac function. In this review, we discussed the relevant factors involved in the regeneration of CMs, generalized in mice, large mammals and human. During different development stages of mammalian hearts, CMs showed several controlling and growth modes on the physiological or pathological state: mitosis, hypertrophy, nuclear polyploidy and multinucleation, amitosis and etc. We also discussed the mechanisms of specific microRNAs implicated in the cardiac development, as well as disease-induced apoptosis in CMs and the process of re-entering cell cycle after injury. It is hoped that this review will contribute to a deeper understanding of therapeutic approaches for myocardial regeneration after injury.