Neural Development最新文献

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mRNAs encoding neurodevelopmental regulators have equal N6-methyladenosine stoichiometry in Drosophila neuroblasts and neurons. 编码神经发育调节因子的mrna在果蝇成神经细胞和神经元中具有相同的n6 -甲基腺苷化学计量。
IF 3.6 3区 生物学
Neural Development Pub Date : 2022-10-15 DOI: 10.1186/s13064-022-00166-4
Josephine D Sami, Robert C Spitale, Michael D Cleary
{"title":"mRNAs encoding neurodevelopmental regulators have equal N6-methyladenosine stoichiometry in Drosophila neuroblasts and neurons.","authors":"Josephine D Sami,&nbsp;Robert C Spitale,&nbsp;Michael D Cleary","doi":"10.1186/s13064-022-00166-4","DOIUrl":"https://doi.org/10.1186/s13064-022-00166-4","url":null,"abstract":"<p><p>N<sup>6</sup>-methyladenosine (m6A) is the most prevalent internal mRNA modification in metazoans and is particularly abundant in the central nervous system. The extent to which m6A is dynamically regulated and whether m6A contributes to cell type-specific mRNA metabolism in the nervous system, however, is largely unknown. To address these knowledge gaps, we mapped m6A and measured mRNA decay in neural progenitors (neuroblasts) and neurons of the Drosophila melanogaster larval brain. We identified 867 m6A targets; 233 of these are novel and preferentially encode regulators of neuroblast proliferation, cell fate-specification and synaptogenesis. Comparison of the neuroblast and neuron m6A transcriptomes revealed that m6A stoichiometry is largely uniform; we did not find evidence of neuroblast-specific or neuron-specific m6A modification. While m6A stoichiometry is constant, m6A targets are significantly less stable in neuroblasts than in neurons, potentially due to m6A-independent stabilization in neurons. We used in vivo quantitative imaging of m6A target proteins in Mettl3 methyltransferase null brains and Ythdf m6A reader overexpressing brains to assay metabolic effects of m6A. Target protein levels decreased in Mettl3 null brains and increased in Ythdf overexpressing brains, supporting a previously proposed model in which m6A enhances translation of target mRNAs. We conclude that m6A does not directly regulate mRNA stability during Drosophila neurogenesis but is rather deposited on neurodevelopmental transcripts that have intrinsic low stability in order to augment protein output.</p>","PeriodicalId":49764,"journal":{"name":"Neural Development","volume":" ","pages":"9"},"PeriodicalIF":3.6,"publicationDate":"2022-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9571443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33512861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
A single-cell transcriptomic atlas of complete insect nervous systems across multiple life stages. 跨越多个生命阶段完整昆虫神经系统的单细胞转录组图谱。
IF 4 3区 生物学
Neural Development Pub Date : 2022-08-24 DOI: 10.1186/s13064-022-00164-6
Marc Corrales, Benjamin T Cocanougher, Andrea B Kohn, Jason D Wittenbach, Xi S Long, Andrew Lemire, Albert Cardona, Robert H Singer, Leonid L Moroz, Marta Zlatic
{"title":"A single-cell transcriptomic atlas of complete insect nervous systems across multiple life stages.","authors":"Marc Corrales, Benjamin T Cocanougher, Andrea B Kohn, Jason D Wittenbach, Xi S Long, Andrew Lemire, Albert Cardona, Robert H Singer, Leonid L Moroz, Marta Zlatic","doi":"10.1186/s13064-022-00164-6","DOIUrl":"10.1186/s13064-022-00164-6","url":null,"abstract":"<p><p>Molecular profiles of neurons influence neural development and function but bridging the gap between genes, circuits, and behavior has been very difficult. Here we used single cell RNAseq to generate a complete gene expression atlas of the Drosophila larval central nervous system composed of 131,077 single cells across three developmental stages (1 h, 24 h and 48 h after hatching). We identify 67 distinct cell clusters based on the patterns of gene expression. These include 31 functional mature larval neuron clusters, 1 ring gland cluster, 8 glial clusters, 6 neural precursor clusters, and 13 developing immature adult neuron clusters. Some clusters are present across all stages of larval development, while others are stage specific (such as developing adult neurons). We identify genes that are differentially expressed in each cluster, as well as genes that are differentially expressed at distinct stages of larval life. These differentially expressed genes provide promising candidates for regulating the function of specific neuronal and glial types in the larval nervous system, or the specification and differentiation of adult neurons. The cell transcriptome Atlas of the Drosophila larval nervous system is a valuable resource for developmental biology and systems neuroscience and provides a basis for elucidating how genes regulate neural development and function.</p>","PeriodicalId":49764,"journal":{"name":"Neural Development","volume":"17 1","pages":"8"},"PeriodicalIF":4.0,"publicationDate":"2022-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9404646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9506145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Single cell RNA-seq analysis reveals temporally-regulated and quiescence-regulated gene expression in Drosophila larval neuroblasts. 单细胞RNA-seq分析揭示了果蝇幼虫神经母细胞中受时间调控和静止调控的基因表达。
IF 4 3区 生物学
Neural Development Pub Date : 2022-08-24 DOI: 10.1186/s13064-022-00163-7
Noah Dillon, Ben Cocanougher, Chhavi Sood, Xin Yuan, Andrea B Kohn, Leonid L Moroz, Sarah E Siegrist, Marta Zlatic, Chris Q Doe
{"title":"Single cell RNA-seq analysis reveals temporally-regulated and quiescence-regulated gene expression in Drosophila larval neuroblasts.","authors":"Noah Dillon, Ben Cocanougher, Chhavi Sood, Xin Yuan, Andrea B Kohn, Leonid L Moroz, Sarah E Siegrist, Marta Zlatic, Chris Q Doe","doi":"10.1186/s13064-022-00163-7","DOIUrl":"10.1186/s13064-022-00163-7","url":null,"abstract":"<p><p>The mechanisms that generate neural diversity during development remains largely unknown. Here, we use scRNA-seq methodology to discover new features of the Drosophila larval CNS across several key developmental timepoints. We identify multiple progenitor subtypes - both stem cell-like neuroblasts and intermediate progenitors - that change gene expression across larval development, and report on new candidate markers for each class of progenitors. We identify a pool of quiescent neuroblasts in newly hatched larvae and show that they are transcriptionally primed to respond to the insulin signaling pathway to exit from quiescence, including relevant pathway components in the adjacent glial signaling cell type. We identify candidate \"temporal transcription factors\" (TTFs) that are expressed at different times in progenitor lineages. Our work identifies many cell type specific genes that are candidates for functional roles, and generates new insight into the differentiation trajectory of larval neurons.</p>","PeriodicalId":49764,"journal":{"name":"Neural Development","volume":"17 1","pages":"7"},"PeriodicalIF":4.0,"publicationDate":"2022-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9404614/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9804335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Early development of the cochlea of the common marmoset, a non-human primate model 普通狨猴耳蜗的早期发育,一种非人类灵长类动物模型
IF 3.6 3区 生物学
Neural Development Pub Date : 2022-05-07 DOI: 10.1186/s13064-022-00162-8
Hosoya, Makoto, Fujioka, Masato, Okahara, Junko, Yoshimatsu, Sho, Okano, Hideyuki, Ozawa, Hiroyuki
{"title":"Early development of the cochlea of the common marmoset, a non-human primate model","authors":"Hosoya, Makoto, Fujioka, Masato, Okahara, Junko, Yoshimatsu, Sho, Okano, Hideyuki, Ozawa, Hiroyuki","doi":"10.1186/s13064-022-00162-8","DOIUrl":"https://doi.org/10.1186/s13064-022-00162-8","url":null,"abstract":"Fine-tuned cochlear development is essential for hearing. Owing to the difficulty in using early human fetal samples, most of our knowledge regarding cochlear development has been obtained from rodents. However, several inter-species differences in cochlear development between rodents and humans have been reported. To bridge these differences, we investigated early otic development of a non-human primate model animal, the common marmoset (Callithrix jacchus). We examined 20 genes involved in early cochlear development and described the critical developmental steps for morphogenesis, which have been reported to vary between rodents and marmosets. The results revealed that several critical genes involved in prosensory epithelium specifications showed higher inter-species differences, suggesting that the molecular process for hair cell lineage acquisition in primates differs considerably from that of rodents. We also observed that the tempo of cochlear development was three times slower in the primate than in rodents. Our data provide new insights into early cochlear development in primates and humans and imply that the procedures used for manipulating rodent cochlear sensory cells cannot be directly used for the research of primate cells due to the intrinsic inter-species differences in the cell fate determination program.","PeriodicalId":49764,"journal":{"name":"Neural Development","volume":"17 16","pages":"6"},"PeriodicalIF":3.6,"publicationDate":"2022-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138518265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 5
DSCAM is differentially patterned along the optic axon pathway in the developing Xenopus visual system and guides axon termination at the target DSCAM在发展中的爪蟾视觉系统中沿视轴突通路有不同的模式,并在目标处引导轴突终止
IF 3.6 3区 生物学
Neural Development Pub Date : 2022-04-15 DOI: 10.1186/s13064-022-00161-9
Santos, Rommel Andrew, Del Rio, Rodrigo, Alvarez, Alexander Delfin, Romero, Gabriela, Vo, Brandon Zarate, Cohen-Cory, Susana
{"title":"DSCAM is differentially patterned along the optic axon pathway in the developing Xenopus visual system and guides axon termination at the target","authors":"Santos, Rommel Andrew, Del Rio, Rodrigo, Alvarez, Alexander Delfin, Romero, Gabriela, Vo, Brandon Zarate, Cohen-Cory, Susana","doi":"10.1186/s13064-022-00161-9","DOIUrl":"https://doi.org/10.1186/s13064-022-00161-9","url":null,"abstract":"The Xenopus retinotectal circuit is organized topographically, where the dorsal–ventral axis of the retina maps respectively on to the ventral-dorsal axis of the tectum; axons from the nasal-temporal axis of the retina project respectively to the caudal-rostral axis of the tectum. Studies throughout the last two decades have shown that mechanisms involving molecular recognition of proper termination domains are at work guiding topographic organization. Such studies have shown that graded distribution of molecular cues is important for topographic mapping. However, the complement of molecular cues organizing topography along the developing optic nerve, and as retinal axons cross the chiasm and navigate towards and innervate their target in the tectum, remains unknown. Down syndrome cell adhesion molecule (DSCAM) has been characterized as a key molecule in axon guidance, making it a strong candidate involved in the topographic organization of retinal fibers along the optic path and at their target. Using a combination of whole-brain clearing and immunohistochemistry staining techniques we characterized DSCAM expression and the projection of ventral and dorsal retinal fibers starting from the eye, following to the optic nerve and chiasm, and into the terminal target in the optic tectum in Xenopus laevis tadpoles. We then assessed the effects of DSCAM on the establishment of retinotopic maps through spatially and temporally targeted DSCAM knockdown on retinal ganglion cells (RGCs) with axons innervating the optic tectum. Highest expression of DSCAM was localized to the ventral posterior region of the optic nerve and chiasm; this expression pattern coincides with ventral fibers derived from ventral RGCs. Targeted downregulation of DSCAM expression on ventral RGCs affected the segregation of medial axon fibers from their dorsal counterparts within the tectal neuropil, indicating that DSCAM plays a role in retinotopic organization. These findings together with previous studies demonstrating cell-autonomous roles for DSCAM during the development of pre- and postsynaptic arbors in the Xenopus retinotectal circuit indicates that DSCAM exerts multiple roles in coordinating axon targeting and structural connectivity in the developing vertebrate visual system.","PeriodicalId":49764,"journal":{"name":"Neural Development","volume":"16 3","pages":""},"PeriodicalIF":3.6,"publicationDate":"2022-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138518275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Correction to: Loss of Neuropilin2a/b or Sema3fa alters olfactory sensory axon dynamics and protoglomerular targeting 更正:Neuropilin2a/b或Sema3fa的缺失改变了嗅觉感觉轴突动力学和原肾小球靶向
IF 3.6 3区 生物学
Neural Development Pub Date : 2022-03-05 DOI: 10.1186/s13064-022-00160-w
Ryan P. Cheng, Puneet Dang, Alemji A. Taku, Yoon Ji Moon, Vi Pham, Xiaohe Sun, Ethan Zhao, J. Raper
{"title":"Correction to: Loss of Neuropilin2a/b or Sema3fa alters olfactory sensory axon dynamics and protoglomerular targeting","authors":"Ryan P. Cheng, Puneet Dang, Alemji A. Taku, Yoon Ji Moon, Vi Pham, Xiaohe Sun, Ethan Zhao, J. Raper","doi":"10.1186/s13064-022-00160-w","DOIUrl":"https://doi.org/10.1186/s13064-022-00160-w","url":null,"abstract":"","PeriodicalId":49764,"journal":{"name":"Neural Development","volume":"17 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2022-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65788803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Enhancer of trithorax/polycomb, Corto, regulates timing of hunchback gene relocation and competence in Drosophila neuroblasts. 三胸/多梳增强子Corto调节果蝇神经母细胞驼背基因重新定位的时间和能力。
IF 3.6 3区 生物学
Neural Development Pub Date : 2022-02-17 DOI: 10.1186/s13064-022-00159-3
Terry L Hafer, Sofiya Patra, Daiki Tagami, Minoree Kohwi
{"title":"Enhancer of trithorax/polycomb, Corto, regulates timing of hunchback gene relocation and competence in Drosophila neuroblasts.","authors":"Terry L Hafer,&nbsp;Sofiya Patra,&nbsp;Daiki Tagami,&nbsp;Minoree Kohwi","doi":"10.1186/s13064-022-00159-3","DOIUrl":"https://doi.org/10.1186/s13064-022-00159-3","url":null,"abstract":"<p><strong>Background: </strong>Neural progenitors produce diverse cells in a stereotyped birth order, but can specify each cell type for only a limited duration. In the Drosophila embryo, neuroblasts (neural progenitors) specify multiple, distinct neurons by sequentially expressing a series of temporal identity transcription factors with each division. Hunchback (Hb), the first of the series, specifies early-born neuronal identity. Neuroblast competence to generate early-born neurons is terminated when the hb gene relocates to the neuroblast nuclear lamina, rendering it refractory to activation in descendent neurons. Mechanisms and trans-acting factors underlying this process are poorly understood. Here we identify Corto, an enhancer of Trithorax/Polycomb (ETP) protein, as a new regulator of neuroblast competence.</p><p><strong>Methods: </strong>We used the GAL4/UAS system to drive persistent misexpression of Hb in neuroblast 7-1 (NB7-1), a model lineage for which the early competence window has been well characterized, to examine the role of Corto in neuroblast competence. We used immuno-DNA Fluorescence in situ hybridization (DNA FISH) in whole embryos to track the position of the hb gene locus specifically in neuroblasts across developmental time, comparing corto mutants to control embryos. Finally, we used immunostaining in whole embryos to examine Corto's role in repression of Hb and a known target gene, Abdominal B (Abd-B).</p><p><strong>Results: </strong>We found that in corto mutants, the hb gene relocation to the neuroblast nuclear lamina is delayed and the early competence window is extended. The delay in gene relocation occurs after hb transcription is already terminated in the neuroblast and is not due to prolonged transcriptional activity. Further, we find that Corto genetically interacts with Posterior Sex Combs (Psc), a core subunit of polycomb group complex 1 (PRC1), to terminate early competence. Loss of Corto does not result in derepression of Hb or its Hox target, Abd-B, specifically in neuroblasts.</p><p><strong>Conclusions: </strong>These results show that in neuroblasts, Corto genetically interacts with PRC1 to regulate timing of nuclear architecture reorganization and support the model that distinct mechanisms of silencing are implemented in a step-wise fashion during development to regulate cell fate gene expression in neuronal progeny.</p>","PeriodicalId":49764,"journal":{"name":"Neural Development","volume":" ","pages":"3"},"PeriodicalIF":3.6,"publicationDate":"2022-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8855600/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39932649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
A subpopulation of astrocyte progenitors defined by Sonic hedgehog signaling. 由音速刺猬信号确定的星形胶质细胞祖细胞亚群。
IF 3.6 3区 生物学
Neural Development Pub Date : 2022-01-14 DOI: 10.1186/s13064-021-00158-w
Ellen C Gingrich, Kendra Case, A Denise R Garcia
{"title":"A subpopulation of astrocyte progenitors defined by Sonic hedgehog signaling.","authors":"Ellen C Gingrich, Kendra Case, A Denise R Garcia","doi":"10.1186/s13064-021-00158-w","DOIUrl":"10.1186/s13064-021-00158-w","url":null,"abstract":"<p><strong>Background: </strong>The molecular signaling pathway, Sonic hedgehog (Shh), is critical for the proper development of the central nervous system. The requirement for Shh signaling in neuronal and oligodendrocyte development in the developing embryo are well established. However, Shh activity is found in discrete subpopulations of astrocytes in the postnatal and adult brain. Whether Shh signaling plays a role in astrocyte development is not well understood.</p><p><strong>Methods: </strong>Here, we use a genetic inducible fate mapping approach to mark and follow a population of glial progenitor cells expressing the Shh target gene, Gli1, in the neonatal and postnatal brain.</p><p><strong>Results: </strong>In the neonatal brain, Gli1-expressing cells are found in the dorsolateral corner of the subventricular zone (SVZ), a germinal zone harboring astrocyte progenitor cells. Our data show that these cells give rise to half of the cortical astrocyte population, demonstrating their substantial contribution to the cellular composition of the cortex. Further, these data suggest that the cortex harbors astrocytes from different lineages. Gli1 lineage astrocytes are distributed across all cortical layers, positioning them for broad influence over cortical circuits. Finally, we show that Shh activity recurs in mature astrocytes in a lineage-independent manner, suggesting cell-type dependent roles of the pathway in driving astrocyte development and function.</p><p><strong>Conclusion: </strong>These data identify a novel role for Shh signaling in cortical astrocyte development and support a growing body of evidence pointing to astrocyte heterogeneity.</p>","PeriodicalId":49764,"journal":{"name":"Neural Development","volume":"17 1","pages":"2"},"PeriodicalIF":3.6,"publicationDate":"2022-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8759290/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10510299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Loss of Neuropilin2a/b or Sema3fa alters olfactory sensory axon dynamics and protoglomerular targeting. Neuropilin2a/b或Sema3fa的缺失会改变嗅觉感觉轴突动力学和原肾小球靶向性。
IF 3.6 3区 生物学
Neural Development Pub Date : 2022-01-03 DOI: 10.1186/s13064-021-00157-x
Ryan P Cheng, Puneet Dang, Alemji A Taku, Yoon Ji Moon, Vi Pham, Xiaohe Sun, Ethan Zhao, Jonathan A Raper
{"title":"Loss of Neuropilin2a/b or Sema3fa alters olfactory sensory axon dynamics and protoglomerular targeting.","authors":"Ryan P Cheng,&nbsp;Puneet Dang,&nbsp;Alemji A Taku,&nbsp;Yoon Ji Moon,&nbsp;Vi Pham,&nbsp;Xiaohe Sun,&nbsp;Ethan Zhao,&nbsp;Jonathan A Raper","doi":"10.1186/s13064-021-00157-x","DOIUrl":"https://doi.org/10.1186/s13064-021-00157-x","url":null,"abstract":"<p><strong>Background: </strong>Olfactory Sensory Neuron (OSN) axons project from the zebrafish olfactory epithelium to reproducible intermediate target locations in the olfactory bulb called protoglomeruli at early stages in development. Two classes of OSNs expressing either OMP or TRPC2 exclusively target distinct, complementary protoglomeruli. Using RNAseq, we identified axon guidance receptors nrp2a and nrp2b, and their ligand sema3fa, as potential guidance factors that are differentially expressed between these two classes of OSNs.</p><p><strong>Methods: </strong>To investigate their role in OSN axon guidance, we assessed the protoglomerular targeting fidelity of OSNs labeled by OMP:RFP and TRPC2:Venus transgenes in nrp2a, nrp2b, or sema3fa mutants. We used double mutant and genetic interaction experiments to interrogate the relationship between the three genes. We used live time-lapse imaging to compare the dynamic behaviors of OSN growth cones during protoglomerular targeting in heterozygous and mutant larvae.</p><p><strong>Results: </strong>The fidelity of protoglomerular targeting of TRPC2-class OSNs is degraded in nrp2a, nrp2b, or sema3fa mutants, as axons misproject into OMP-specific protoglomeruli and other ectopic locations in the bulb. These misprojections are further enhanced in nrp2a;nrp2b double mutants suggesting that nrp2s work at least partially in parallel in the same guidance process. Results from genetic interaction experiments are consistent with sema3fa acting in the same biological pathway as both nrp2a and nrp2b. Live time-lapse imaging was used to examine the dynamic behavior of TRPC2-class growth cones in nrp2a mutants compared to heterozygous siblings. Some TRPC2-class growth cones ectopically enter the dorsal-medial region of the bulb in both groups, but in fully mutant embryos, they are less likely to correct the error through retraction. The same result was observed when TRPC2-class growth cone behavior was compared between sema3fa heterozygous and sema3fa mutant larvae.</p><p><strong>Conclusions: </strong>Our results suggest that nrp2a and nrp2b expressed in TRPC2-class OSNs help prevent their mixing with axon projections in OMP-specific protoglomeruli, and further, that sema3fa helps to exclude TRPC2-class axons by repulsion from the dorsal-medial bulb.</p>","PeriodicalId":49764,"journal":{"name":"Neural Development","volume":" ","pages":"1"},"PeriodicalIF":3.6,"publicationDate":"2022-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8725463/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39643320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 4
The oligodendrocyte-enriched orphan G protein-coupled receptor Gpr62 is dispensable for central nervous system myelination. 少突胶质细胞富集的孤儿G蛋白偶联受体Gpr62在中枢神经系统髓鞘形成中是必不可少的。
IF 3.6 3区 生物学
Neural Development Pub Date : 2021-11-29 DOI: 10.1186/s13064-021-00156-y
Curtis M Hay, Stacey Jackson, Stanislaw Mitew, Daniel J Scott, Matthias Koenning, AeSoon L Bensen, Helena Bujalka, Trevor J Kilpatrick, Ben Emery
{"title":"The oligodendrocyte-enriched orphan G protein-coupled receptor Gpr62 is dispensable for central nervous system myelination.","authors":"Curtis M Hay,&nbsp;Stacey Jackson,&nbsp;Stanislaw Mitew,&nbsp;Daniel J Scott,&nbsp;Matthias Koenning,&nbsp;AeSoon L Bensen,&nbsp;Helena Bujalka,&nbsp;Trevor J Kilpatrick,&nbsp;Ben Emery","doi":"10.1186/s13064-021-00156-y","DOIUrl":"https://doi.org/10.1186/s13064-021-00156-y","url":null,"abstract":"<p><strong>Background: </strong>Myelination is a highly regulated process in the vertebrate central nervous system (CNS) whereby oligodendrocytes wrap axons with multiple layers of insulating myelin in order to allow rapid electrical conduction. Establishing the proper pattern of myelin in neural circuits requires communicative axo-glial interactions, however, the molecular interactions that occur between oligodendrocytes and axons during developmental myelination and myelin maintenance remain to be fully elucidated. Our previous work identified G protein-coupled receptor 62 (Gpr62), an uncharacterized orphan g-protein coupled receptor, as being selectively expressed by mature oligodendrocytes within the CNS, suggesting a potential role in myelination or axoglial interactions. However, no studies to date have assessed the functional requirement for Gpr62 in oligodendrocyte development or CNS myelination.</p><p><strong>Methods: </strong>To address this, we generated a knockout mouse strain lacking the Gpr62 gene. We assessed CNS myelination during both postnatal development and adulthood using immunohistochemistry, electron microscopy and western blot. In addition, we utilized AAV-mediated expression of a tagged Gpr62 in oligodendrocytes to determine the subcellular localization of the protein in vivo.</p><p><strong>Results: </strong>We find that virally expressed Gpr62 protein is selectively expressed on the adaxonal myelin layer, suggestive of a potential role for Gpr62 in axo-myelinic signaling. Nevertheless, Gpr62 knockout mice display normal oligodendrocyte numbers and apparently normal myelination within the CNS during both postnatal development and adulthood.</p><p><strong>Conclusions: </strong>We conclude that in spite of being well-placed to mediate neuronal-oligodendrocyte communications, Gpr62 is overall dispensable for CNS myelination.</p>","PeriodicalId":49764,"journal":{"name":"Neural Development","volume":" ","pages":"6"},"PeriodicalIF":3.6,"publicationDate":"2021-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8630896/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39789281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
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