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The generation of various subtypes of neurons and glial cells at the right time and place is crucial for the proper development
of the vertebrate CNS. Although the mechanisms and factors for the regulation of neuronal diversity in the CNS have been well
studied, the mechanisms regulating the sequential production of neuronal and glial cells from neural precursors remain poorly
understood. This study shows that Tcf3, a member of the Lef/Tcf family of proteins, is required to inhibit the premature oligodendroglial
fate specification of spinal cord precursors using the transgenic zebrafish, which expresses a dominant repressor form of
Tcf3 under the control of a heat-shock inducible promoter. In addition, the data revealed that Tcf3 function in oligodendroglial
fate specification is mediated independently of canonical Wnt signaling. Altogether, these results show a novel function for
Tcf3 in regulating the timing of oligodendroglial fate specification in the spinal cord. 相似文献
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《Developmental neurobiology》2017,77(10):1188-1205
Adult neurogenesis is a complex, presumably conserved phenomenon in vertebrates with a broad range of variations regarding neural progenitor/stem cell niches, cellular composition of these niches, migratory patterns of progenitors and so forth among different species. Current understanding of the reasons underlying the inter‐species differences in adult neurogenic potential, the identification and characterization of various neural progenitors, characterization of the permissive environment of neural stem cell niches and other important aspects of adult neurogenesis is insufficient. In the last decade, zebrafish has emerged as a very useful model for addressing these questions. In this review, we have discussed the present knowledge regarding the neural stem cell niches in adult zebrafish brain as well as their cellular and molecular attributes. We have also highlighted their similarities and differences with other vertebrate species. In the end, we shed light on some of the known intrinsic and extrinsic factors that are assumed to regulate the neurogenic process in adult zebrafish brain. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1188–1205, 2017 相似文献
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成年斑马鱼(Danio rerio)具有很强的脊髓损伤后自主修复的能力, 但目前其机制不明。为了研究斑马鱼中脑组织对脊髓再生的影响, 文章应用成年斑马鱼脊髓损伤模型, 采用实时定量PCR方法和原位杂交技术, 检测了斑马鱼脑中胶质细胞源性神经营养因子(gdnf)和一氧化氮合酶(nos)基因在脊髓损伤后4 h、12 h、6 d、11 d的表达情况, 展示了这两种基因在斑马鱼脑内不同核团的动态表达变化。结果显示, 成年斑马鱼脊髓损伤后, 神经营养因子gdnf基因在损伤急性期(4 h、12 h)和神经修复期(6 d、11 d)于斑马鱼脑内呈现显著性升高(P<0.05),而一氧化氮合酶基因nos的表达于损伤急性期显著性升高 (P<0.05), 随后下降, 并在修复期 (11 d)显著降低(P<0.05)。这表明, 脊髓损伤后, 高表达gdnf基因同时低表达nos基因的脑环境给脊髓损伤提供了良好的神经再生微环境, 从而可能促进轴突的再生长及运动能力的恢复。 相似文献
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Little is known about the role of the hindbrain during development of spinal network activity. We set out to identify the activity patterns of reticulospinal (RS) neurons of the hindbrain in fictively swimming (paralyzed) zebrafish larvae. Simultaneous recordings of RS neurons and spinal motoneurons revealed that these were coactive during spontaneous fictive swim episodes. We characterized four types of RS activity patterns during fictive swimming: (i) a spontaneous pattern of discharges resembling evoked high-frequency spiking during startle responses to touch stimuli, (ii) a rhythmic pattern of excitatory postsynaptic potentials (EPSPs) whose frequency was similar to the motoneuron EPSP frequency during swim episodes, (iii) an arrhythmic pattern consisting of tonic firing throughout swim episodes, and (iv) RS cell activity uncorrelated with motoneuron activity. Despite lesions to the rostral spinal cord that prevented ascending spinal axons from entering the hindbrain (normally starting at approximately 20 h), RS neurons continued to display the aforementioned activity patterns at day 3. However, removal of the caudal portion of the hindbrain prior to the descent of RS axons left the spinal cord network unable to generate the rhythmic oscillations normally elicited by application of N-methyl-d-aspartate (NMDA), but in approximately 40% of cases chronic incubation in NMDA maintained rhythmic activity. We conclude that there is an autonomous embryonic hindbrain network that is necessary for proper development of the spinal central pattern generator, and that the hindbrain network can partially develop independently of ascending input. 相似文献
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Yi-Ping Yan Bradley T. Lang Raghu Vemuganti†‡ Robert J. Dempsey† 《Journal of neurochemistry》2009,109(6):1624-1635
We investigated intracerebral hemorrhage (ICH)-induced lateral migration of neuroblasts and the mechanism underlying this migration. ICH model was induced by collagenase injection into the striatum of adult wild-type and osteopontin (OPN) knockout mice. In the wild-type mice, the lateral migration of neuroblasts from the ipsislateral subventricular zone (SVZ) towards the hematoma started at day 3 and continued up to day 28 after ICH. In addition to migrating towards the hematoma, neuroblasts also migrated to the area of ipsilateral striatum remote to the hematoma. The migrating neuroblasts were closely associated with activated astrocytes and blood vessels in the injured striatum. Following ICH, the expression of OPN was up-regulated in the ipsilateral striatum from day 1 to day 28. In vitro , OPN treatment did not affect the proliferation of neural progenitors, but enhanced the trans-well and radial migration of neural progenitors. In vivo , OPN deficiency did not affect the proliferation of neural progenitors in the SVZ. However, following ICH a significant decrease in lateral neuroblast migration was observed in the OPN knockout mice compared with the wild-type mice. These results suggest that increased OPN expression in the injured striatum plays a significant role in the lateral migration of neuroblasts following ICH. 相似文献
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钙离子作为广泛存在的细胞内信使物质,在动物胚胎早期发育过程中扮演重要角色.为了研究钙离子在斑马鱼胚胎发育过程中的空间分布和浓度变化,采用Fluo-4和Indo-1作为钙离子指示剂,利用激光共聚焦和双波长荧光比例成像技术,对斑马鱼胚胎第一次卵裂过程中的钙信号进行了详细的跟踪观察.在第一次卵裂过程中,斑马鱼胚胎的动物极顶端首先出现高钙斑,然后在分裂沟部位出现高浓度的钙信号,这一信号在卵裂过程中持续存在.利用Indo-1双波长荧光比例成像对上述过程中钙离子的时空分布进行了定量测定,表明,胞内钙离子在卵裂开始之前是均匀分布的,随着分裂沟的出现,其附近区域的钙浓度显著升高,而胞内其他区域的钙浓度则保持不变.双波长荧光比例成像排除了荧光染料分布不均匀造成的干扰,为钙信号与胚胎分裂的密切关系提供了确凿的定量依据. 相似文献
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Development of the central nervous system (CNS) requires progressive differentiation of neural stem cells, which generate
a variety of neural progenitors with distinct properties and differentiation potentials in a spatiotemporally restricted manner.
The underlying mechanisms of neural progenitor diversification during development started to be unraveled over the past years.
We have addressed these questions by v-myc immortalization method and generation of neural progenitor clones. These clones
are served as in vitro models of neural differentiation and cellular tools for transplantation in animal models of neurological disorders including
spinal cord injury. In this review, we will discuss features of two neural progenitor types (radial glia and GABAergic interneuron
progenitor) and diversification even within each progenitor type. We will also discuss pathophysiology of spinal cord injury
and our ongoing research to address both motor and sensory malfunctions by transplantation of these neural progenitors. 相似文献
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《Developmental neurobiology》2017,77(11):1269-1307
The knifefish Apteronotus leptorhynchus exhibits indeterminate growth throughout adulthood. This phenomenon extends to the spinal cord, presumably through the continuous addition of new neurons and glial cells. However, little is known about the developmental dynamics of cells added during adult growth. The present work characterizes the structural and functional development of the adult spinal cord in this model organism through a comprehensive quantitative analysis of the spatial and temporal dynamics of new cells at various developmental stages. This analysis, based on a novel statistical mapping approach, revealed within the adult spinal cord a wide distribution of both mitotically active and quiescent Sox2‐expressing stem/progenitor cells (SPCs). While such cells are particularly concentrated within the ependymal layer near the central canal, the majority of them reside in the parenchyma, resembling the distribution of SPCs observed in the mammalian spinal cord. The active SPCs in the adult knifefish spinal cord give rise to transit amplifying progenitor cells that undergo a few additional mitotic divisions before developing into Hu C/D+ neurons and S100+ glial cells. There is no evidence of long‐distance migration of the newborn cells. The persistence of cell proliferation and differentiation, combined with low levels of apoptosis, leads to a continuous addition of cells to the existing tissue. Newly generated neurons have functional and behavioral relevance, as indicated by the integration of axons of new electromotor neurons into the electric organ of these weakly electric fish. This results in a gradual increase in the amplitude of the electric organ discharge during adult development. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1269–1307, 2017 相似文献
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A new culturing strategy improves functional neuronal development of human neural progenitor cells 总被引：1，自引：0，他引：1
Grit Schaarschmidt† Sabine Schewtschik Robert Kraft† Florian Wegner‡ Jens Eilers† Johannes Schwarz Hartmut Schmidt† 《Journal of neurochemistry》2009,109(1):238-247
Cell replacement therapies that rely on in vitro differentiation of human neural progenitor cells are a promising strategy to compensate the progressive cell loss in neurodegenerative disorders like Parkinson's disease. We and others observed, that the functional differentiation of progenitors in standard differentiation medium remains limited. The aim of the present study was to optimize neuronal in vitro differentiation by mimicking the physiological shift from depolarizing to hyperpolarizing conditions that occurs during early brain development. Differentiation was initiated using a depolarizing high potassium- and low sodium-containing medium. Subsequently, the high potassium-containing medium was replaced by a hyperpolarizing medium containing low potassium and high sodium concentrations. This two-phase strategy significantly promoted the expression of neuronal markers, enhanced neurite growth, enlarged sodium inward currents, and increased action potential firing. Thus, depolarizing followed by hyperpolarizing culture conditions enable developing human neural progenitor cells to adopt more mature functional qualities. 相似文献
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Sheng‐Jia Lin Ching‐Chi Chiu Tsu‐Lin Ma Tu‐Hsueh Yeh Yi‐Chuan Cheng 《Developmental neurobiology》2015,75(5):452-462
Multiple epigenetic factors play a critical role in cell proliferation and differentiation. However, their function in embryogenesis, especially in neural development, is currently unclear. The Trithorax group (TrxG) homolog KMT2A (MLL1) is an important epigenetic regulator during development and has an especially well‐defined role in hematopoiesis. Translocation and aberrant expression of KMT2A is often observed in many tumors, indicating its proto‐oncogenic character. Here, we show that Kmt2a was essential for neural development in zebrafish embryos. Disrupting the expression of Kmt2a using morpholino antisense oligonucleotides and a dominant‐negative variant resulted in neurogenic phenotypes, including downregulated proliferation of neural progenitors, premature differentiation of neurons, and impaired gliogenesis. This study therefore revealed a novel function of Kmt2a in cell proliferation and differentiation, providing further insight into the function of TrxG proteins in neural development and brain tumors. © 2014 Wiley Periodicals, Inc. Develop Neurobiol 75: 452–462, 2015 相似文献
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Mammals fail in sensory and motor recovery following spinal cord injury due to lack of axonal regrowth below the level of injury as well as an inability to reinitiate spinal neurogenesis. However, some anamniotes including the zebrafish Danio rerio exhibit both sensory and functional recovery even after complete transection of the spinal cord. The adult zebrafish is an established model organism for studying regeneration following spinal cord injury, with sensory and motor recovery by 6 weeks post-injury. To take advantage of in vivo analysis of the regenerative process available in the transparent larval zebrafish as well as genetic tools not accessible in the adult, we use the larval zebrafish to study regeneration after spinal cord transection. Here we demonstrate a method for reproducibly and verifiably transecting the larval spinal cord. After transection, our data shows sensory recovery beginning at 2 days post-injury (dpi), with the C-bend movement detectable by 3 dpi and resumption of free swimming by 5 dpi. Thus we propose the larval zebrafish as a companion tool to the adult zebrafish for the study of recovery after spinal cord injury. 相似文献
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Jacob E. Montgomery Sarah Wahlstrom‐Helgren Timothy D. Wiggin Brittany M. Corwin Christina Lillesaar Mark A. Masino 《Developmental neurobiology》2018,78(8):807-827
Serotonin (5HT) is a modulator of many vital processes in the spinal cord (SC), such as production of locomotion. In the larval zebrafish, intraspinal serotonergic neurons (ISNs) are a source of spinal 5HT that, despite the availability of numerous genetic and optical tools, has not yet been directly shown to affect the spinal locomotor network. In order to better understand the functions of ISNs, we used a combination of strategies to investigate ISN development, morphology, and function. ISNs were optically isolated from one another by photoconverting Kaede fluorescent protein in individual cells, permitting morphometric analysis as they developed in vivo. ISN neurite lengths and projection distances exhibited the greatest amount of change between 3 and 4 days post‐fertilization (dpf) and appeared to stabilize by 5 dpf. Overall ISN innervation patterns were similar between cells and between SC regions. ISNs possessed rostrally‐extending neurites resembling dendrites and a caudally‐extending neurite resembling an axon, which terminated with an enlarged growth cone‐like structure. Interestingly, these enlargements remained even after neurite extension had ceased. Functionally, application of exogenous 5HT reduced spinally‐produced motor nerve bursting. A selective 5HT reuptake inhibitor and ISN activation with channelrhodopsin‐2 each produced similar effects to 5HT, indicating that spinally‐intrinsic 5HT originating from the ISNs has an inhibitory effect on the spinal locomotor network. Taken together this suggests that the ISNs are morphologically mature by 5 dpf and supports their involvement in modulating the activity of the spinal locomotor network. © 2018 Wiley Periodicals, Inc. Develop Neurobiol, 2018 相似文献
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The anatomy of the developing zebrafish spinal cord is relatively simple but, despite this simplicity, it generates a sequence of three patterns of locomotive behaviors. The first behavior exhibited is spontaneous movement, then touch‐evoked coiling, and finally swimming. Previous studies in zebrafish have suggested that spontaneous movements occur independent of supraspinal input and do not require chemical neurotransmission, while touch‐evoked coiling and swimming depend on glycinergic neurotransmission as well as supraspinal input. In contrast, studies in other vertebrate preparations have shown that spontaneous movement requires glycine and other neurotransmitters and that later behaviors do not require supraspinal input. Here, we use lesion analysis combined with high‐speed kinematic analysis to re‐examine the role of glycine and supraspinal input in each of the three behaviors. We find that, similar to other vertebrate preparations, supraspinal input is not essential for spontaneous movement, touch‐evoked coiling, or swimming behavior. Moreover, we find that blockade of glycinergic neurotransmission decreases the rate of spontaneous movement and impairs touch‐evoked coiling and swimming, suggesting that glycinergic neurotransmission plays critical yet distinct roles for individual patterns of locomotive behaviors. © 2006 Wiley Periodicals, Inc. J Neurobiol, 2006 相似文献