Developmental Neurobiology最新文献

{"title":"Editorial overview: Microtubules in nervous system development","authors":"Frank Bradke, Antonina Roll-Mecak","doi":"10.1002/dneu.22817","DOIUrl":"10.1002/dneu.22817","url":null,"abstract":"The ability of the nervous system to process information depends on the complex and precise organization of highly ramified and polarized cells such as neurons and glia. The microtubule cytoskeleton is crucial for these cells to attain their elaborate morphologies and to maintain the polarized trafficking of cargo that are required for their communication. This special issue of Developmental Neurobiology brings together reviews and original work focused on how neurons and glia build and maintain their polarized, complex microtubule arrays, how they orchestrate the trafficking of organelles and vesicles, and how they remodel their microtubule cytoskeleton in response to injury. The issue starts with two reviews focused on how microtubule arrays are built and maintained in neurons and glia. These cells pose particular challenges because they need to assemble the microtubule arrays with different morphologies and dynamics in their soma and distal processes and thus rely on decentralized mechanisms of microtubule nucleation. Lüders focuses on recent advances in our understanding of the molecular mechanisms of microtubule nucleation in axons and dendrites to generate arrays with different organization and polarities. This specialization of the microtubule cytoskeleton for transmitting (axon) and receiving (dendrite) information is central to neuronal circuitry (Lüders, 2021). Weigel and colleagues present an overview of microtubule organization of glial cells in the brain– – oligodendrocytes, astrocytes, and microglia, and highlight the many outstanding questions that still remain unanswered in the field: the molecular pathways for microtubule nucleation in distal processes, how trafficking is directed and how these cells build unique, complex structures such as the myelin sheet (Weigel et al., 2021). Trafficking is a key process in neurons, where organelles move along microtubules in the axon and dendrites. In their review, Cheng and Sheng describe how mitochondria are transported in the axon during development and maturation. Interestingly, they highlight recent work about how mitochondria motility changes with aging and present links to neurodegenerative, injured and regenerative stages of the nervous system (Cheng & Sheng, 2021). While we have reached a good understanding of microtubule dynamics, structure and trafficking events in neurons we still know relatively little about the different tubulin isotypes expressed in the developing brain. The article from the Kneussel lab helps to fill this important gap by presenting the tubulin isotypes that are differentially expressed in the developing mouse brain and cultured primary neurons (Hausrat et al., 2021). Next, Moutin and colleagues focus on the role of tubulin posttranslational modifications that is, the tubulin code in regulating microtubule dynamics, neuronal differentiation, plasticity, and transport and highlight the role of the tubulin code in many pathologies of the nervous system (Moutin ","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2021-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/dneu.22817","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38895098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuronal androgen receptor is required for activity dependent enhancement of peripheral nerve regeneration","authors":"Patricia J. Ward,&nbsp;Rachel A. Davey,&nbsp;Jeffrey D. Zajac,&nbsp;Arthur W. English","doi":"10.1002/dneu.22826","DOIUrl":"10.1002/dneu.22826","url":null,"abstract":"<p>Neuronal activity after nerve injury can enhance axon regeneration and the restoration of function. The mechanism for this enhancement relies in part on hormone receptors, and we previously demonstrated that systemic androgen receptor antagonism blocked the effect of exercise or electrical stimulation on enhancing axon regeneration after nerve injury in both sexes. Here, we tested the hypothesis that the site of this androgen receptor signaling is both neuronal and involves the classical, genomic signaling pathway. In vivo, dorsal root ganglion neurons successfully regenerate in response to activity-dependent neuronal activation, and conditional deletion of the DNA-binding domain of the androgen receptor in adults blocks this effect in males and females. Motoneurons in males and females also respond in this manner, but we also observed a sex difference. In vitro, cultured sensory dorsal root ganglion neurons respond to androgens via traditional androgen receptor signaling mechanisms leading to enhanced neurite growth and did not respond to a testosterone conjugate that is unable to cross the cell membrane. Given our previous observation of a requirement for activity-dependent androgen receptor signaling to promote regeneration in both sexes, we interpret our results to indicate that genomic neuronal androgen receptor signaling is required for activity-dependent axon regeneration in both sexes.</p>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2021-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/dneu.22826","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38887851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engrailed-2 is a cell autonomous regulator of neurogenesis in cultured hippocampal neural stem cells","authors":"Madel Durens,&nbsp;Mai Soliman,&nbsp;James Millonig,&nbsp;Emanuel DiCicco-Bloom","doi":"10.1002/dneu.22824","DOIUrl":"10.1002/dneu.22824","url":null,"abstract":"<p>Abnormalities in genes that regulate early brain development are known risk factors for neurodevelopmental disorders. <i>Engrailed-2</i> (<i>En2</i>) is a homeodomain transcription factor with established roles in cerebellar patterning. <i>En2</i> is highly expressed in the developing mid-hindbrain region, and <i>En2</i> knockout (KO) mice exhibit major deficits in mid-hindbrain structures. However, <i>En2</i> is also expressed in forebrain regions including the hippocampus, but its function is unknown. Previous studies have shown that the hippocampus of <i>En2</i>-KO mice exhibits reductions in its volume and cell numbers due to aberrant neurogenesis. Aberrant neurogenesis is due, in part, to noncell autonomous effects, specifically, reductions of innervating norepinephrine fibers from the locus coeruleus. In this study, we investigate possible cell autonomous roles of <i>En2</i> in hippocampal neurogenesis. We examine proliferation, survival, and differentiation using cultures of hippocampal neurospheres of P7 wild-type (WT) and <i>En2</i>-KO hippocampal neural progenitor cells (NPCs). At 7 days, <i>En2</i>-KO neurospheres were larger on average than WT spheres and exhibited 2.5-fold greater proliferation and 2-fold increase in apoptotic cells, similar to in vivo KO phenotype. Further, <i>En2</i>-KO cultures exhibited 40% less cells with neurite projections, suggesting decreased differentiation. Lastly, reestablishing <i>En2</i> expression in <i>En2</i>-KO NPCs rescued excess proliferation. These results indicate that <i>En2</i> functions in hippocampal NPCs by inhibiting proliferation and promoting survival and differentiation in a cell autonomous manner. More broadly, this study suggests that <i>En2</i> impacts brain structure and function in diverse regions outside of the mid-hindbrain.</p>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2021-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/dneu.22824","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25588371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Persistent organic pollutants at the synapse: Shared phenotypes and converging mechanisms of developmental neurotoxicity","authors":"Sarah E. Latchney,&nbsp;Ania K. Majewska","doi":"10.1002/dneu.22825","DOIUrl":"10.1002/dneu.22825","url":null,"abstract":"<p>The developing nervous system is sensitive to environmental and physiological perturbations in part due to its protracted period of prenatal and postnatal development. Epidemiological and experimental studies link developmental exposures to persistent organic pollutants (POPs) including polychlorinated biphenyls, polychlorinated dibenzo-<i>p</i>-dioxins, polybrominated diphenyl ethers, and benzo(a)pyrene to increased risk for neurodevelopmental disorders in children. Mechanistic studies reveal that many of the complex cellular processes that occur during sensitive periods of rapid brain development are cellular targets for developmental neurotoxicants. One area of research interest has focused on synapse formation and plasticity, processes that involve the growth and retraction of dendrites and dendritic spines. For each chemical discussed in this review, we summarize the morphological and electrophysiological data that provide evidence that developmental POP exposure produces long-lasting effects on dendritic morphology, spine formation, glutamatergic and GABAergic signaling systems, and synaptic transmission. We also discuss shared intracellular mechanisms, with a focus on calcium and thyroid hormone homeostasis, by which these chemicals act to modify synapses. We conclude our review highlighting research gaps that merit consideration when characterizing synaptic pathology elicited by chemical exposure. These gaps include low-dose and nonmonotonic dose-response effects, the temporal relationship between dendritic growth, spine formation, and synaptic activity, excitation-inhibition balance, hormonal effects, and the need for more studies in females to identify sex differences. By identifying converging pathological mechanisms elicited by POP exposure at the synapse, we can define future research directions that will advance our understanding of these chemicals on synapse structure and function.</p>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2021-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/dneu.22825","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25598778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"White matter alterations in young children with prenatal alcohol exposure","authors":"Preeti Kar,&nbsp;Jess E. Reynolds,&nbsp;Melody N. Grohs,&nbsp;W. Ben Gibbard,&nbsp;Carly McMorris,&nbsp;Christina Tortorelli,&nbsp;Catherine Lebel","doi":"10.1002/dneu.22821","DOIUrl":"10.1002/dneu.22821","url":null,"abstract":"<p>Prenatal alcohol exposure (PAE) can lead to cognitive, behavioural, and social–emotional challenges. Previous neuroimaging research has identified structural brain alterations in newborns, older children, adolescents, and adults with PAE; however, little is known about brain structure in young children. Extensive brain development occurs during early childhood; therefore, understanding the neurological profiles of young children with PAE is critical for early identification and effective intervention. We studied 54 children (5.21 ± 1.11 years; 27 males) with confirmed PAE (94% also had other prenatal exposures, 74% had adverse postnatal experiences) compared with 54 age- and sex-matched children without PAE. Children underwent diffusion tensor imaging between 2 and 7 years of age. Mean fractional anisotropy (FA) and mean diffusivity (MD) were obtained for 10 major white matter tracts. Univariate analyses of covariance were used to test group differences (PAE vs. control) controlling for age and sex. The PAE group had higher FA in the genu of the corpus callosum and lower MD in the bilateral uncinate fasciculus. The PAE group also had lower tract volume in the corpus callosum, the bilateral inferior fronto-occipital fasciculi, and the right superior longitudinal fasciculus. Our findings align with studies of newborns with PAE reporting lower diffusivity, but contrast those in older populations with PAE, which consistently report lower FA and higher MD. Further research is needed to understand trajectories of white matter development and how our results of higher FA/lower MD in young children connect with lower FA/higher MD observed at older ages.</p>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2021-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/dneu.22821","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25571673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune cells enhance Zika virus-mediated neurologic dysfunction in brain of mice with humanized immune systems","authors":"Anthony N. van den Pol,&nbsp;Xue Zhang,&nbsp;Stephen E. Maher,&nbsp;Alfred L. M. Bothwell","doi":"10.1002/dneu.22820","DOIUrl":"10.1002/dneu.22820","url":null,"abstract":"<p>Zika virus (ZIKV) can generate a number of neurological dysfunctions in infected humans. Here, we tested the potential of human immune cells to protect against ZIKV infection in genetically humanized MISTRG mice. FACS analysis showed robust reconstitution of the mouse spleen with human T cells. Peripheral ZIKV inoculation resulted in infection within the brains of MISTRG mice. Mice that were reconstituted with human peripheral blood mononuclear cells (PBMC) showed a more rapid lethal response to ZIKV than the control mice lacking these immune cells. Immunocytochemical analysis of T cell markers CD3, CD45, or CD8 showed strong T cell presence in the brain, together with robust infection by ZIKV particularly in the excitatory pyramidal and granule neurons of the hippocampus. Infection was also found in cortex, striatum, the dopamine neurons of the substantia nigra, and other brain loci. Infection was considerably less in other regions such as the septum and hypothalamus. These data support the perspective that, rather than exerting a protective function, T cells may underlie some ZIKV-mediated neuropathology in the brain.</p>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2021-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/dneu.22820","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25557326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Data Driven Methods to Balance Fairness and Profit in Ride-Pooling","authors":"Naveen Raman","doi":"10.13016/G78E-DNEU","DOIUrl":"https://doi.org/10.13016/G78E-DNEU","url":null,"abstract":"","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2021-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49219456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using organoids to study human brain development and evolution","authors":"Wai-Kit Chan,&nbsp;Rana Fetit,&nbsp;Rosie Griffiths,&nbsp;Helen Marshall,&nbsp;John O. Mason,&nbsp;David J. Price","doi":"10.1002/dneu.22819","DOIUrl":"10.1002/dneu.22819","url":null,"abstract":"<p>Recent advances in methods for making cerebral organoids have opened a window of opportunity to directly study human brain development and disease, countering limitations inherent in non-human-based approaches. Whether freely patterned, guided into a region-specific fate or fused into assembloids, organoids have successfully recapitulated key features of in vivo neurodevelopment, allowing its examination from early to late stages. Although organoids have enormous potential, their effective use relies on understanding the extent of their limitations in accurately reproducing specific processes and components in the developing human brain. Here we review the potential of cerebral organoids to model and study human brain development and evolution and discuss the progress and current challenges in their use for reproducing specific human neurodevelopmental processes.</p>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2021-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/dneu.22819","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25522010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tools and approaches for analyzing the role of mitochondria in health, development and disease using human cerebral organoids","authors":"Michał Liput,&nbsp;Chiara Magliaro,&nbsp;Zuzanna Kuczynska,&nbsp;Valery Zayat,&nbsp;Arti Ahluwalia,&nbsp;Leonora Buzanska","doi":"10.1002/dneu.22818","DOIUrl":"10.1002/dneu.22818","url":null,"abstract":"<p>Mitochondria are cellular organelles involved in generating energy to power various processes in the cell. Although the pivotal role of mitochondria in neurogenesis was demonstrated (first in animal models), very little is known about their role in human embryonic neurodevelopment and its pathology. In this respect human-induced pluripotent stem cells (hiPSC)-derived cerebral organoids provide a tractable, alternative model system of the early neural development and disease that is responsive to pharmacological and genetic manipulations, not possible to apply in humans. Although the involvement of mitochondria in the pathogenesis and progression of neurodegenerative diseases and brain dysfunction has been demonstrated, the precise role they play in cell life and death remains unknown, compromising the development of new mitochondria-targeted approaches to treat human diseases. The cerebral organoid model of neurogenesis and disease in vitro provides an unprecedented opportunity to answer some of the most fundamental questions about mitochondrial function in early human neurodevelopment and neural pathology. Largely an unexplored territory due to the lack of tools and approaches, this review focuses on recent technological advancements in fluorescent and molecular tools, imaging systems, and computational approaches for quantitative and qualitative analyses of mitochondrial structure and function in three-dimensional cellular assemblies—cerebral organoids. Future developments in this direction will further facilitate our understanding of the important role or mitochondrial dynamics and energy requirements during early embryonic development. This in turn will provide a further understanding of how dysfunctional mitochondria contribute to disease processes.</p>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2021-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/dneu.22818","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25493612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microglia regulate synaptic development and plasticity","authors":"Megumi Andoh,&nbsp;Ryuta Koyama","doi":"10.1002/dneu.22814","DOIUrl":"10.1002/dneu.22814","url":null,"abstract":"<p>Synapses are fundamental structures of neural circuits that transmit information between neurons. Thus, the process of neural circuit formation via proper synaptic connections shapes the basis of brain functions and animal behavior. Synapses continuously undergo repeated formation and elimination throughout the lifetime of an organism, reflecting the dynamics of neural circuit function. The structural transformation of synapses has been described mainly in relation to neural activity-dependent strengthening and weakening of synaptic functions, that is, functional plasticity of synapses. An increasing number of studies have unveiled the roles of microglia, brain-resident immune cells that survey the brain parenchyma with highly motile processes, in synapse formation and elimination as well as in regulating synaptic function. Over the past 15 years, the molecular mechanisms underlying microglia-dependent regulation of synaptic plasticity have been thoroughly studied, and researchers have reported that the disruption of microglia-dependent regulation causes synaptic dysfunction that leads to brain diseases. In this review, we will broadly introduce studies that report the roles of microglia in synaptic plasticity and the possible underlying molecular mechanisms.</p>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2021-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/dneu.22814","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25365995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}