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Retinoic acid, an essential component of the RP organizer, promotes the spatio-temporal segregation of dorsal neural fates

ABSTRACT: Retinoic acid, an essential component of the RP organizer, promotes the spatio-temporal segregation of dorsal neural fates

PROVIDER: PRJNA1088098 | ENA |

REPOSITORIES: ENA

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Retinoic acid, an essential component of the RP organizer, promotes the spatio-temporal segregation of dorsal neural fates

Project description:Dorsal neural tube-derived retinoic acid promotes the end of neural crest production and transition into a definitive roof plate. Here we analyze how this impacts the segregation of central and peripheral lineages, a process essential for tissue patterning and function. Localized in-ovo inhibition of retinoic acid activity followed by single cell transcriptomics unraveled a comprehensive list of differentially expressed genes relevant to these processes. Importantly, progenitors co-expressed neural crest, roof plate and di1 interneuron markers indicating a failure in proper lineage segregation. Furthermore, we found that separation between roof plate and dI1 interneurons is mediated by Notch activity downstream of retinoic acid, highlighting their critical role in establishing the roof plate-dI1 boundary. Within the peripheral branch, where absence of retinoic acid resulted in neural crest production and emigration extending into the roof plate stage, sensory progenitors failed to separate from melanocytes leading to formation of a common glia-melanocyte cell with aberrant migratory patterns. Together, we uncover and characterize a molecular mechanism responsible for segregation of dorsal neural fates during development.

2024-09-23 | GSE261603 | GEO

Variation of human neural stem cells generating organizer states in vitro before committing to cortical excitatory or inhibitory neuronal fates [mouse RNAseq]

Project description:Better understanding the progression of neural stem cells (NSCs) in the developing cerebral cortex is important for modeling neurogenesis and defining the pathogenesis of neuropsychiat-ric disorders. Here we used RNA-sequencing, cell imaging and lineage tracing of mouse and human in vitro NSCs to model the generation of cortical neuronal fates. We show that con-served signaling mechanisms regulate the acute transition from proliferative NSCs to commit-ted glutamatergic excitatory neurons. As human telencephalic NSCs developed from pluripo-tentcy in vitro, they first transitioned through organizer states that spatially pattern the cortex before generating glutamatergic precursor fates. NSCs derived from multiple human pluripotent lines varied in these early states leading differentially to dorsal or ventral telencephalic fates. This work furthers systematic analysis of the earliest patterning events that generate the major neuronal trajectories of the human telencephalon. The gene amplitudes for the GWCoGAPS patterns in this data can be found in the supplemental files.

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Variation of human neural stem cells generating organizer states in vitro before committing to cortical excitatory or inhibitory neuronal fates [human RNAseq #2]

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Variation of human neural stem cells generating organizer states in vitro before committing to cortical excitatory or inhibitory neuronal fates [human RNAseq #1]

2020-04-15 | GSE144156 | GEO

Genomic Analysis of the Xenopus Organizer

Project description:Studies of the Xenopus organizer have laid the foundation for our understanding of the conserved signaling pathways that pattern vertebrate embryos during gastrulation. Here, we use this wealth of knowledge as leverage in the design and analysis of a genomic visualization of organizer-related gene transcription. Using ectopic expression of the two major activities of the organizer, BMP and Wnt inhibition, as well as endogenous tissues, we generate a focused set of samples that represent different aspects of organizer signaling. The genomic expression values of each sample are then measured with oligonucleotide arrays. From this data, genes regulated by organizer signaling are selected and then clustered by their patterns of regulation. A new GO biological process annotation of the Xenopus genome allows us to rapidly identify clusters that are highly enriched for known gastrula patterning genes. Within these clusters, we can predict the expression patterns of unknown genes with remarkable accuracy, leading to the discovery of new organizer-related gastrula stage expression patterns for 19 genes. Moreover, the patterns of gene response observed within these clusters allow us to parse apart the contributions of BMP and Wnt inhibition in organizer function. We find that the majority of gastrula patterning genes respond transcriptionally to these activities according to only a few stereotyped patterns, allowing us to describe suites of genes that are likely to share similar regulatory mechanisms. These suites of genes demonstrate a mechanism where BMP inhibition initiates the organizer program before gastrulation, and Wnt inhibition maintains and drives the organizer program during gastrulation. Keywords: development, organizer, noggin, dkk-1, xenopus, gastrulation

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Lesion Segregation

Project description:Liver Cancer Evolution - Lesion segregation

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Retinitis pigmentosa (RP) mouse cone transcriptom change with Txnip treatment

Project description:Purpose: To identifiy mRNA changes in retinitis pigmentosa (RP) cone photoreceptors with Txnip overexpression treatment, which improved RP cone survival and visual acuity. Methods: two RP mouse strains, rd1 and Rho-/-, were injected with AAV-Txnip or AAV-H2BGFP control subretinally at P0. Retinas were dissected out at P21 for rd1 and P90 for Rho-/-. 1,000 H2BGFP labeled cones per retina sample were FACS sorted out, and subject for RNA-sequencing. Results: >1,400 genes in P21 rd1 and >700 genes in Rho-/- were found differentially expressed with Txnip treatment. Conclusions: 25 genes are in common between P21 rd1 and P90 Rho-/- with Txnip treatment. On this list, notably, three mitochondrial Electron Transport Chain (ETC) genes were up-regulated.

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Variation of human neural stem cells generating organizer states in vitro before committing to cortical excitatory or inhibitory neuronal fates

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Project description:Variation of human neural stem cells generating organizer states in vitro before committing to cortical excitatory or inhibitory neuronal fates

| PRJNA603839 | ENA

RNA-seq analysis to assess transcriptional effects of Rp mutations in wing imaginal discs and their dependence on Xrp1

Project description:Since the putative transcription factor Xrp1 gene is required for many aspects of Rp+/- phenotypes, we sought to define what transcriptional changes occur in Rp+/- wing discs and their dependence on Xrp1. We identified 257 genes whose transcripts were significantly altered in the same direction in two Rp+/- genotypes, most of which depended on Xrp1. The results show that Xrp1 regulates a significant transcriptional response in Rp+/- genotypes.

2018-08-20 | GSE112864 | GEO

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