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Patterning ganglionic eminences in developing human brain organoids using morphogen gradient inducing device

ABSTRACT: Patterning ganglionic eminences in developing human brain organoids using morphogen gradient inducing device

PROVIDER: PRJNA1022059 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR26213573_1.fastq.gz	Fastqsanger.gz
	SRR26213573_2.fastq.gz	Fastqsanger.gz
	SRR26213574_1.fastq.gz	Fastqsanger.gz
	SRR26213574_2.fastq.gz	Fastqsanger.gz
	SRR26213575_1.fastq.gz	Fastqsanger.gz

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Patterning ganglionic eminences in developing human brain organoids using morphogen gradient inducing device

Project description:In early neurodevelopment, the central nervous system is established through the coordination of various neural organizers directing tissue patterning and cell differentiation. Better recapitulation of morphogen gradient production and signaling will be crucial for establishing improved developmental models of the brainin vitro. Here, we developed a method by assembling polydimethylsiloxane (PDMS) devices capable of generating a sustained chemical gradient to produce patterned brain organoids, which we termedMorphogen-gradientInducedBrainOrganoids (MIBOs). At 3.5 weeks, MIBOs replicated Dorsal-Ventral patterning observed in the Ganglionic Eminence (GE). Analysis of matured MIBOs through single-cell RNA sequencing revealed distinct Dorsal GE derived CALB2+ interneurons (INs), Medium Spiny Neurons (MSNs), and MGE derived cell types. Finally, we demonstrate long term culturing capabilities with MIBOs maintaining stable neural activity in cultures grown up to 5.5 months. MIBOs demonstrate a versatile approach for generating spatially patterned brain organoids for embryonic development and disease modeling.

2024-02-14 | GSE244281 | GEO

Gene expression profile of cells with unfit Wnt morphogen gradient during cell competition

Project description:Morphogen signalling forms an activity gradient and instructs cell identities in a signalling strength-dependent manner to pattern developing tissues. However, developing tissues also undergo dynamic morphogenesis, which may produce cells with unfit morphogen signalling and consequent noisy morphogen gradient. Here we show that a cell competition-related system corrects such noisy morphogen gradients. Zebrafish imaging analyses of the Wnt/β-catenin signalling gradient, which acts as a morphogen to establish embryonic anterior-posterior patterning, revealed that unfit cells with abnormal Wnt/β-catenin activity spontaneously appear and produce noise in the gradient. Communication between unfit and neighbouring fit cells via cadherin proteins stimulates apoptosis of the unfit cells by activating Smad signalling and reactive oxygen species production. This unfit cell elimination is required for proper Wnt/β-catenin gradient formation and consequent anterior-posterior patterning. Because this gradient controls patterning not only in the embryo but also in adult tissues, this system may support tissue robustness and disease prevention.

2019-09-15 | GSE133526 | GEO

Gene expression profile of neighboring cells of cells with unfit Wnt morphogen gradient during cell competition

2024-11-15 | GSE254439 | GEO

Morphogen Stimulated Endocytic Recycling Drives Cytoneme Loading for Mammalian Tissue Patterning

Project description:Morphogen Stimulated Endocytic Recycling Drives Cytoneme Loading for Mammalian Tissue Patterning

| PRJNA1011884 | ENA

Morphogen Stimulated Endocytic Recycling Drives Cytoneme Loading for Mammalian Tissue Patterning

Project description:During development, morphogens build tissues by instructing cell fate across long distances. Directly visualizing morphogen transport in situ has been unfeasible, so the molecular mechanisms ensuring successful morphogen delivery remain unclear. To tackle this longstanding problem, we developed a mouse model for compromised Sonic Hedgehog (SHH) morphogen delivery and discovered that endocytic recycling promotes SHH loading into signaling filopodia called cytonemes. We optimized methods to preserve in vivo cytonemes for advanced microscopy and show endogenously-expressed SHH localized to cytonemes in developing mouse neural tubes. Depletion of SHH from neural tube cytonemes alters neuronal cell fates and compromises neurodevelopment. Mutation of the filopodial motor Myosin 10 (MYO10) reduces cytoneme length and density, which corrupts neuronal signaling activity of both SHH and WNT. Combined, these results demonstrate that cytoneme-based signal transport provides essential contributions to morphogen dispersion during mammalian tissue development and suggest MYO10 is a key regulator of cytoneme function.

2024-01-02 | GSE242161 | GEO

Soh2020 - Spatio-temporal morphogen gradient and BMP signaling

Project description:This model couples BMP morphogen gradient formation with Smad signaling in zebrafish and reproduces Fig.3B of the referenced paper. mBMP4 diffuses and forms a morphogen gradient in the host tissue where differential signal transduction kinetics for pSmad2 versus pSmad5 lead to narrow (pSmad2) versus wide (pSmad5) signal activity ranges in response to the same morphogen gradient (mBMP4) as input. The model file is in MorpheusML format and can be opened in the free, open-source multicellular modeling software Morpheus (https://morpheus.gitlab.io) to simulate the time course (movie) of the spatio-temporal dynamics. Further optional plots of the radial solution profile and the time courses of mean concentrations over the domain are included and temporarily inactivated in the model file, in section Analysis.

2021-10-06 | MODEL2012070002 | BioModels

Bulk RNA-seq of the human fetal neocortex, lateral ganglionic eminence and medial ganglionic eminence at 7, 9, 11 and 20 post-conceptional weeks

Project description:Deep transcriptional profiling of the human neocortex, lateral ganglionic eminence (LGE) and medial ganglionic eminences (MGE), from 7 to 20 post-conceptional weeks (pcw), for de novo lincRNAs discovery and to establish a unique coding and non-coding gene signature for the three different regions.

2021-05-13 | E-MTAB-8893 | biostudies-arrayexpress

WNT signaling memory is required for ACTIVIN to function as a morphogen

Project description:It has now become clear that the process of fate specification during early embryogenesis is mediated by a handful of key signaling pathways. However, how the temporal and spatial integration of these signals plays out to give rise to self-organization of tissues remains obscure. Here we use artificial human gastruloids and quantitative single-cell analysis to dissect the temporal integration of two key pathways WNT and ACTIVIN that along with BMP control gastrulation and primitive streak patterning in model systems. We showed that ACTIVIN elicits a transient signaling response, as well as a transient induction of differentiation. However, unlike BMP and WNT, ACTIVIN cannot induce stable primitive streak formation and mesodermal patterning. Pre-exposure to WNT switches the response of cells to ACTIVIN whereby it becomes a concentration dependent morphogen. This provides evidence for WNT signaling memory that occurs at the transcriptional level and not as a modifier of ACTIVIN signaling dynamics.

2018-10-22 | GSE111717 | GEO

Morphogen-signalling modifying factors in Panarthropoda

Project description:morphogen-signalling modifying factors in Panarthropoda

| PRJEB28122 | ENA

Otx2 controls regional patterning within the MGE and regional identity of the septum [ChIP-Seq]

Project description:The Otx2 homeobox transcription factor is essential for gastrulation and early neural development. We generated Otx2 conditional knockout (cKO) mice to investigate its roles in telencephalon development after E9.0. We conducted transcriptional profiling and in situ hybridization to identify genes de-regulated in Otx2 cKO ventral forebrain. In parallel, we used ChIP-seq to identify enhancer elements, OTX2 binding motif, and which de-regulated genes are likely direct targets of Otx2 transcriptional regulation. We found that Otx2 was essential in septum specification; regulation of Fgf signaling in the rostral telencephalon; and medial ganglionic eminence (MGE) patterning, neurogenesis, and oligodendrogenesis. Within the MGE, Otx2 was required for ventral but not dorsal identity; this is the first demonstration of a transcription factor that contributes to regional patterning within the MGE. Microdissected subpallium (septum, MGE, and LGE ) from wildtype E12.5 CD-1 embryos was used in three independentanti-OTX2 ChIP-seq experiments.

2015-06-10 | E-GEOD-69724 | biostudies-arrayexpress

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