DeCoN: Genome-wide Analysis of In Vivo Transcriptional Dynamics during Pyramidal Neuron Fate Selection in Neocortex

Molyneaux, Bradley J.; Goff, Loyal A.; Brettler, Andrea C.; Chen, Hsu-Hsin; Brown, Juliana; Hrvatin, Siniša; Rinn, John L.; Arlotta, Paola

doi:10.1016/j.neuron.2015.12.011

Cited by 74 publications

(119 citation statements)

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“…LncRNAs are well known for their tissue-specific expression patterns compared to protein-coding genes, and JensenShannon (JS) divergence analysis reveals high tissue-specificity scores of lncRNAs expressed from different human tissues (Cabili et al 2011). The same analysis also suggests considerable cellular specificity of lncRNAs among different neuronal cell types (Molyneaux et al 2015). We further performed JS divergence analysis for brain mRNAs and lncRNAs from the brain samples and found that the majority of lncRNAs and mRNAs scored lower than 0.25, which was lower than the lncRNA scores from the studies mentioned above.…”

Section: Lncrna Expression In Rhesus Macaque Brain Is Highly Similar mentioning

confidence: 94%

Annotation and cluster analysis of spatiotemporal- and sex-related lncRNA expression in rhesus macaque brain

Liu

Wang

Chen³

et al. 2017

Genome Res.

102

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Long noncoding RNAs (lncRNAs) mediate important epigenetic regulation in a wide range of biological processes and diseases. We applied comprehensive analyses of RNA-seq and CAGE-seq (cap analysis of gene expression and sequencing) to characterize the dynamic changes in lncRNA expression in rhesus macaque (Macaca mulatta) brain in four representative age groups. We identified 18 anatomically diverse lncRNA modules and 14 mRNA modules representing spatial, age, and sex specificities. Spatiotemporal-and sex-biased changes in lncRNA expression were generally higher than those observed in mRNA expression. A negative correlation between lncRNA and mRNA expression in cerebral cortex was observed and functionally validated. Our findings offer a fresh insight into spatial-, age-, and sex-biased changes in lncRNA expression in macaque brain and suggest that the changes represent a previously unappreciated regulatory system that potentially contributes to brain development and aging.

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Section: Lncrna Expression In Rhesus Macaque Brain Is Highly Similar mentioning

confidence: 94%

Annotation and cluster analysis of spatiotemporal- and sex-related lncRNA expression in rhesus macaque brain

Liu

Wang

Chen³

et al. 2017

Genome Res.

102

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“…For example, only 29 lncRNAs are conserved between zebrafish and humans (49). Strikingly, in the same study, the phenotype in zebrafish following functional inactivation of conserved lncRNAs can be rescued by an orthologous gene from either mice development of the cerebral cortex (64,68). Profiling endogenous lncRNA expression may therefore highlight the diversity of genetically defined cell types and their potential to promote disease.…”

Section: Evolutionary Conservation Of Lncrnasmentioning

confidence: 86%

“…This feature renders animal models well suited for the study of lncRNAs, given that lncRNA expression is more tissue and cell type specific than is protein-coding gene expression (5,10,64). When compared with cultured cells, material derived from animals is generally less abundant and more time-consuming to generate.…”

Section: Animal Models and Lncrna Profilingmentioning

confidence: 99%

“…Modern techniques available for genomics research, such as RNA-seq, provide an unbiased, high-throughput approach to investigating endogenous lncRNA expression and to discovering and assembling novel lncRNAs de novo (64). lncRNA expresplexity of these species can be advantageous for investigating the role of lncRNAs in highly conserved biological processes, whose dysfunction may contribute to human disease.…”

Section: Animal Models and Lncrna Profilingmentioning

confidence: 99%

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Investigating long noncoding RNAs using animal models

Feyder¹,

Goff²

2016

Journal of Clinical Investigation

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“…Several studies have identified a multitude of transcription factors and regulatory genes that are specific to callosal neurons, regardless of layer identity, as well as layer-specific callosal gene expression. These studies have also revealed that callosal neurons form a genetically heterogeneous population, even within a single cortical layer (Molyneaux et al, 2009;Molyneaux et al, 2015). However, the precise function of these genes in specifying a callosal fate or mediating subsequent gene expression/functions that contribute to callosal development, remains to be determined.…”

Section: Callosal Cell Specification and Migrationmentioning

confidence: 99%

Contralateral targeting of the corpus callosum

Fenlon¹

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During development, the brain establishes billions of precise connections in order to perform its myriad functions. The largest of these connections in placental mammals is the corpus callosum, which is a large bundle of axons linking the two cortical hemispheres of the brain. Absence or gross malformation of this structure is a relatively common developmental disorder in humans, producing symptoms ranging from severe to mild cognitive, emotional and motor deficits. However, recent evidence suggests that the corpus callosum can also display subtle malformations that are not visible with traditional magnetic resonance imaging methods, and that these may be involved in neurodevelopmental disorders such as autism and schizophrenia. The possibility of callosal misconnectivity arising independently of the widely-studied process of midline crossing highlights the need to investigate other less well-understood stages of callosal development. One such process that may be disrupted after normal midline crossing of the corpus callosum is contralateral targeting, where axons must locate, innervate and stabilize in their appropriate contralateral cortical targets.This thesis focuses on understanding the normal process of contralateral targeting, as well as the nature of its dependence on neuronal activity and the molecular mechanisms that regulate it. To investigate these topics, diverse approaches including in utero electroporation, stereotaxic brain injection, sensory deprivation paradigms, tissuespecific RNA extraction and RNA sequencing were used in the mouse somatosensory cortex model system of callosal connectivity. Novel patterns and processes of normal contralateral targeting were identified, as well as distinct periods of region-specific activitydependent and -independent axonal exuberance. Contralateral callosal targeting was also shown to be not just dependent on neuronal activity, but rather a balance of spatially symmetric activity between the two cortical hemispheres. The molecular mechanisms underlying activity-dependent and -independent stages of contralateral callosal targeting were also investigated, and a novel technique to extract RNA from an electroporated population of cell bodies and/or their callosal axons was developed to facilitate this study in the future.These results constitute fundamental insights into the process of contralateral callosal targeting, as well as some of the mechanisms that may lead to its disruption. This work provides solid foundations for future studies to build upon, and may ultimately help us to better understand subtle human disorders of neuronal connectivity.3

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DeCoN: Genome-wide Analysis of In Vivo Transcriptional Dynamics during Pyramidal Neuron Fate Selection in Neocortex

Cited by 74 publications

References 0 publications

Annotation and cluster analysis of spatiotemporal- and sex-related lncRNA expression in rhesus macaque brain

Annotation and cluster analysis of spatiotemporal- and sex-related lncRNA expression in rhesus macaque brain

Investigating long noncoding RNAs using animal models

Contralateral targeting of the corpus callosum

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