Search Results (16)

Neuromechanobiology has emerged as a multidisciplinary field at the interface of neuroscience and mechanobiology, aiming to elucidate how mechanical forces influence the development, organization, and function of the nervous system. This review offers a comprehensive overview of the historical evolution of the discipline, its molecular and biophysical foundations, and the experimental strategies employed to investigate it. Recent advances have revealed the pivotal roles of substrate stiffness, mechanical signaling, and force transduction in neural stem proliferation, axon guidance, synapse formation, and neural circuit maturation. All these effects originate at the molecular level and extend to the mesoscopic scale. Disrupted mechanotransduction has been increasingly implicated in neurodevelopmental disorders and neurodegenerative diseases, underscoring its clinical relevance. Key unresolved questions and future directions are also highlighted, with emphasis on the need for integrative approaches to decipher the complex interplay between mechanical forces and neural function. Full article

Pharyngeal cartilage, derived from neural crest cells (NCCs), undergoes complex morphogenesis driven by signals from the pharyngeal endoderm. However, the molecular mechanisms governing NCC proliferation and differentiation in response to endoderm-derived signals remain poorly understood. Here, we investigate the role of klf5a, a zinc-finger transcription factor expressed in pharyngeal endodermal pouches, in zebrafish pharyngeal cartilage development. Knockdown of klf5a using morpholinos minimally affected cranial NCC specification and migration but significantly impaired their proliferation and differentiation in the pharyngeal region. Notably, klf5a deficiency reduced expression of fgfbp2b, a modulator of FGF signaling, in the pharyngeal endoderm. Co-injection of klf5a mRNA rescued the cartilage defects, but injection of fgfbp2b mRNA alone failed to restore normal cartilage morphogenesis, suggesting that fgfbp2b is not the sole mediator of klf5a’s effects. These findings indicate that klf5a regulates endodermal signaling to direct NCC-derived pharyngeal cartilage formation, likely through multiple downstream targets including fgfbp2b. This study provides insights into the complex molecular network underlying craniofacial development and highlights potential therapeutic targets for craniofacial disorders. Full article

The rationale for age-structured population migration system models lies in the significant impact of age patterns on migration dynamics, as age-specific migration rates exhibit distinct regularities and are influenced by life course transitions, socio-economic conditions, and demographic structures. Based on artificial neural networks, this article proposes a class of population models with age structure described by partial differential equations to predict the future trends of regional population changes. The population migration rate, as a complex nonlinear feature, can be trained through artificial neural networks, providing a population approximation system. By employing semigroup theory, we establish the well-posedness of the proposed system. It is shown that the solution of the approximation system can converge to that of the original system in the sense of the $L^2$-norm. Finally, several simulation experiments are provided to verify the effectiveness of the population forecasting model. Full article

Collective migration underlies key developmental and disease processes in vertebrates. Mathematical models describing collective migration can shed light on emergent patterns arising from simple mechanisms. In this paper, a mathematical model for collective migration is given for arbitrary numbers and types of individuals using principles outlined as a set of assumptions, such as the assumed preference for individuals to be “close but not too close" to others. The model is then specified to the case of two species with arbitrary numbers of individuals in each species. A particular form of signal response is used that may be parameterized based on experiments involving two or three agents. In its simplest form, the model describes two species of individuals that emit distinct signals, distinguishes between them, and exhibits responses unique to the type by moving according to signal gradients in various planar regions, a situation described as "mixotaxis". Beyond this simple form, initial conditions and boundary conditions are altered to simulate specific, additional in vitro as well as in vivo dynamics. The behaviors that were specifically accounted for include motility, directed migration, and a functional response to a signal. Ultimately, the paper’s results highlight the ability of a single framework for signal and response to account for patterns seen in multi-species systems, in particular the emergent self-organization seen in the embryonic development of placodal cells, which display chase-and-run behavior, flocking behavior, herding behavior, and the splitting of a herd, depending on initial conditions. Numerical experiments focus around the primary example of neural crest and placodal cell “chase-and-run” and “flocking” behaviors; the model reproduces the separation of placodal cells into distinct clumps, as described in the literature for neural crest and placodal cell development. This model was developed to describe a heterogeneous environment and can be expanded to capture other biological systems with one or more distinct species. Full article

Harmonic mechanisms orchestrate neurogenesis in the healthy brain within specific neurogenic niches, which generate neurons from neural stem cells as a homeostatic mechanism. These newly generated neurons integrate into existing neuronal circuits to participate in different brain tasks. Despite the mechanisms that protect the mammalian brain, this organ is susceptible to many different types of damage that result in the loss of neuronal tissue and therefore in alterations in the functionality of the affected regions. Nevertheless, the mammalian brain has developed mechanisms to respond to these injuries, potentiating its capacity to generate new neurons from neural stem cells and altering the homeostatic processes that occur in neurogenic niches. These alterations may lead to the generation of new neurons within the damaged brain regions. Notwithstanding, the activation of these repair mechanisms, regeneration of neuronal tissue within brain injuries does not naturally occur. In this review, we discuss how the different neurogenic niches respond to different types of brain injuries, focusing on the capacity of the progenitors generated in these niches to migrate to the injured regions and activate repair mechanisms. We conclude that the search for pharmacological drugs that stimulate the migration of newly generated neurons to brain injuries may result in the development of therapies to repair the damaged brain tissue. Full article

The pathological mechanisms of neural tube defects (NTDs) are not yet fully understood. Although the dysregulation of histone modification in NTDs is recognized, it remains to be fully elucidated on a genome-wide level. We profiled genome-wide H3K27me3 and H3K27ac occupancy by CUT&Tag in neural tissues from ICR mouse embryos with benzo[a]pyrene (BaP)-induced NTDs (250 mg kg⁻¹) at E9.5. Furthermore, we performed RNA sequencing (RNA-seq) to investigate the regulation of histone modifications on gene expressions. Gene ontology and KEGG analysis were conducted to predict pathways involved in the development of NTDs. Our analysis of histone 3 lysine 27 modification in BaP-NTD neural tissues compared to BaP-nonNTD revealed 6045 differentially trimethylated regions and 3104 acetylated regions throughout the genome, respectively. The functional analysis identified a number of pathways uniquely enriched for BaP-NTD embryos, including known neurodevelopment related pathways such as anterior/posterior pattern specification, ephrin receptor signaling pathway, neuron migration and neuron differentiation. RNA-seq identified 423 differentially expressed genes (DEGs) between BaP-NTD and BaP-nonNTD group. The combination analysis of CUT&Tag and RNA-seq found that 55 DEGs were modified by H3K27me3 and 25 by H3K27ac in BaP-NTD, respectively. In the transcriptional regulatory network, transcriptional factors including Srsf1, Ume6, Zbtb7b, and Cad were predicated to be involved in gene expression regulation. In conclusion, our results provide an overview of histone modifications during neural tube closure and demonstrate a key role of genome-wide alterations in H3K27me3 and H3K27ac in NTDs corresponding with changes in transcription profiles. Full article

Brain organoids can reproduce the regional three-dimensional (3D) tissue structure of human brains, following the in vivo developmental trajectory at the cellular level; therefore, they are considered to present one of the best brain simulation model systems. By briefly summarizing the latest research concerning brain organoid construction methods, the basic principles, and challenges, this review intends to identify the potential role of the physiological electric field (EF) in the construction of brain organoids because of its important regulatory function in neurogenesis. EFs could initiate neural tissue formation, inducing the neuronal differentiation of NSCs, both of which capabilities make it an important element of the in vitro construction of brain organoids. More importantly, by adjusting the stimulation protocol and special/temporal distributions of EFs, neural organoids might be created following a predesigned 3D framework, particularly a specific neural network, because this promotes the orderly growth of neural processes, coordinate neuronal migration and maturation, and stimulate synapse and myelin sheath formation. Thus, the application of EF for constructing brain organoids in a3D matrix could be a promising future direction in neural tissue engineering. Full article

Cerebral stroke remains one of the leading causes of death worldwide. Ischemic stroke caused by the sudden loss of blood flow in brain is the major type of cerebral stroke. In addition to necrotic cell death in the ischemic core region, neuronal apoptosis is usually observed in the ischemic penumbra. Pnn, a multi-functional protein, participates in cellular proliferation, migration, differentiation, apoptosis as well as cell–cell interaction through its abilities in regulating gene transcription and mRNA processing. Our recent studies have demonstrated that Pnn has a cell type-specific distribution manner in neural cells under ischemic injury and plays a protective role in astrocytes against ischemic stress. In this study, we generated an inducible neuron-specific Pnn deficiency mouse model to further investigate the physiological role of Pnn in neurons. To directly examine the role of neuronal Pnn in ischemic stress, four weeks after induction of Pnn deficiency in neurons, middle cerebral artery occlusion (MCAO) was applied to induce cerebral ischemia/reperfusion in mice. In the cerebrum and hippocampus with neuronal Pnn depletion, the expression of SRSF2, a mRNA splicing regulator, was increased, while the expression of SRSF1, a functional antagonist of SRSF2, was reduced. Expression levels of ROS generators (NOX-1 and NOX-2) and antioxidant proteins (GR, HO-1, NQO-1) were upregulated in brain tissue with loss of neuronal Pnn, echoing an increase in oxidized proteins in cortical and hippocampal neurons. Furthermore, the expression of DNA damage marker, p53bp1, was found in the choroid plexus of mice with neuronal Pnn depletion. In mice with MCAO, compared to wild type mice, both increased cerebral infarcted area and elevated expressions of proapoptotic proteins were found in mice with neuronal Pnn depletion. In conclusion, Pnn deficiency increases oxidative stress in neurons and exacerbates cerebral ischemia/reperfusion injury in mice. Full article

Neural precursors originating in the subventricular zone (SVZ), the largest neurogenic region of the adult brain, migrate several millimeters along a restricted migratory pathway, the rostral migratory stream (RMS), toward the olfactory bulb (OB), where they differentiate into interneurons and integrate into the local neuronal circuits. Migration of SVZ-derived neuroblasts in the adult brain differs in many aspects from that in the embryonic period. Unlike in that period, postnatally-generated neuroblasts in the SVZ are able to divide during migration along the RMS, as well as they migrate independently of radial glia. The homophilic mode of migration, i.e., using each other to move, is typical for neuroblast movement in the RMS. In addition, it has recently been demonstrated that specifically-arranged blood vessels navigate SVZ-derived neuroblasts to the OB and provide signals which promote migration. Here we review the development of vasculature in the presumptive neurogenic region of the rodent brain during the embryonic period as well as the development of the vascular scaffold guiding neuroblast migration in the postnatal period, and the significance of blood vessel reorganization during the early postnatal period for proper migration of RMS neuroblasts in adulthood. Full article

Neurogenesis in the adult state is the process of new neuron formation. This relatively infrequent phenomenon comprises four stages: cell proliferation, cell migration, differentiation, and the integration of these cells into an existing circuit. Recent reports suggest that neurogenesis can be found in different regions of the Central Nervous System (CNS), including the spinal cord (SC). This process can be observed in physiological settings; however, it is more evident in pathological conditions. After spinal cord injury (SCI), the activation of microglial cells and certain cytokines have shown to exert different modulatory effects depending on the presence of inflammation and on the specific region of the injury site. In these conditions, microglial cells and cytokines are considered to play an important role in the regulation of neurogenesis after SCI. The purpose of this article is to present an overview on neural progenitor cells and neurogenic and non-neurogenic zones as well as the cellular and molecular regulation of neurogenesis. Additionally, we will briefly describe the recent advances in the knowledge of neurogenesis after SCI. Full article

A prolonged developmental timeline for GABA (γ-aminobutyric acid)-expressing inhibitory neurons (GABAergic interneurons) is an amplified trait in larger, gyrencephalic animals. In several species, the generation, migration, and maturation of interneurons take place over several months, in some cases persisting after birth. The late integration of GABAergic interneurons occurs in a region-specific pattern, especially during the early postnatal period. These changes can contribute to the formation of functional connectivity and plasticity, especially in the cortical regions responsible for higher cognitive tasks. In this review, we discuss GABAergic interneuron development in the late gestational and postnatal forebrain. We propose the protracted development of interneurons at each stage (neurogenesis, neuronal migration, and network integration), as a mechanism for increased complexity and cognitive flexibility in larger, gyrencephalic brains. This developmental feature of interneurons also provides an avenue for environmental influences to shape neural circuit formation. Full article

Lattice degeneration involves thinning of the retina that occurs over time. Here we performed an immunohistological study of tissue sections of human peripheral retinal lattice degeneration to investigate if retinal pigment epithelium (RPE) cells are involved in the pathogenesis of this condition. In two cases of retinal detachment with a large tear that underwent vitreous surgery, retinal lattice degeneration tissue specimens were collected during surgery. In the obtained specimens, both whole mounts and horizontal section slices were prepared, and immunostaining was then performed with hematoxylin and antibodies against glial fibrillary acidic protein (GFAP), RPE-specific protein 65 kDa (RPE65), pan-cytokeratin (pan-CK), and CK18. Hematoxylin staining showed no nuclei in the center of the degenerative lesion, thus suggesting the possibility of the occurrence of apoptosis. In the degenerative lesion specimens, GFAP staining was observed in the center, RPE65 staining was observed in the slightly peripheral region, and pan-CK staining was observed in all areas. However, no obvious CK18 staining was observed. In a monkey retina used as the control specimen of a normal healthy retina, no RPE65 or pan-CK staining was observed in the neural retina. Our findings suggest that migration, proliferation, and differentiation of RPE cells might be involved in the repair of retinal lattice degeneration. Full article

Oligodendrocytes are the myelinating cells of the central nervous system (CNS). These cells arise during the embryonic development by the specification of the neural stem cells to oligodendroglial progenitor cells (OPC); newly formed OPC proliferate, migrate, differentiate, and mature to myelinating oligodendrocytes in the perinatal period. It is known that progesterone promotes the proliferation and differentiation of OPC in early postnatal life through the activation of the intracellular progesterone receptor (PR). Progesterone supports nerve myelination after spinal cord injury in adults. However, the role of progesterone in embryonic OPC differentiation as well as the specific PR isoform involved in progesterone actions in these cells is unknown. By using primary cultures obtained from the embryonic mouse spinal cord, we showed that embryonic OPC expresses both PR-A and PR-B isoforms. We found that progesterone increases the proliferation, differentiation, and myelination potential of embryonic OPC through its PR by upregulating the expression of oligodendroglial genes such as neuron/glia antigen 2 (NG2), sex determining region Y-box9 (SOX9), myelin basic protein (MBP), 2′,3′-cyclic-nucleotide 3′-phosphodiesterase (CNP1), and NK6 homeobox 1 (NKX 6.1). These effects are likely mediated by PR-B, as they are blocked by the silencing of this isoform. The results suggest that progesterone contributes to the process of oligodendrogenesis during prenatal life through specific activation of PR-B. Full article

We have previously observed the predominant expression of nucleoporin 62-like (Nup62l) mRNA in the pharyngeal region of zebrafish, which raises the question whether Nup62l has important implications in governing the morphogenesis of pharyngeal arches (PA) in zebrafish. Herein, we explored the functions of Nup62l in PA development. The disruption of Nup62l with a CRISPR/Cas9-dependent gene knockout approach led to defective PA, which was characterized by a thinned and shortened pharyngeal region and a significant loss of pharyngeal cartilages. During pharyngeal cartilage formation, prechondrogenic condensation and chondrogenic differentiation were disrupted in homozygous nup62l-mutants, while the specification and migration of cranial neural crest cells (CNCCs) were unaffected. Mechanistically, the impaired PA region of nup62l-mutants underwent extensive apoptosis, which was mainly dependent on activation of p53-dependent apoptotic pathway. Moreover, aberrant activation of a series of apoptotic pathways in nup62l-mutants is closely associated with the inactivation of Wnt/β-catenin signaling. Thus, these findings suggest that the regulation of Wnt/β-catenin activity by Nup62l is crucial for PA formation in zebrafish. Full article

As an active microwave sensor, synthetic aperture radar (SAR) has the characteristic of all-day and all-weather earth observation, which has become one of the most important means for high-resolution earth observation and global resource management. Ship detection in SAR images is also playing an increasingly important role in ocean observation and disaster relief. Nowadays, both traditional feature extraction methods and deep learning (DL) methods almost focus on improving ship detection accuracy, and the detection speed is neglected. However, the speed of SAR ship detection is extraordinarily significant, especially in real-time maritime rescue and emergency military decision-making. In order to solve this problem, this paper proposes a novel approach for high-speed ship detection in SAR images based on a grid convolutional neural network (G-CNN). This method improves the detection speed by meshing the input image, inspired by the basic thought of you only look once (YOLO), and using depthwise separable convolution. G-CNN is a brand new network structure proposed by us and it is mainly composed of a backbone convolutional neural network (B-CNN) and a detection convolutional neural network (D-CNN). First, SAR images to be detected are divided into grid cells and each grid cell is responsible for detection of specific ships. Then, the whole image is input into B-CNN to extract features. Finally, ship detection is completed in D-CNN under three scales. We experimented on an open SAR Ship Detection Dataset (SSDD) used by many other scholars and then validated the migration ability of G-CNN on two SAR images from RadarSat-1 and Gaofen-3. The experimental results show that the detection speed of our proposed method is faster than the existing other methods, such as faster-regions convolutional neural network (Faster R-CNN), single shot multi-box detector (SSD), and YOLO, under the same hardware environment with NVIDIA GTX1080 graphics processing unit (GPU) and the detection accuracy is kept within an acceptable range. Our proposed G-CNN ship detection system has great application values in real-time maritime disaster rescue and emergency military strategy formulation. Full article