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Analysis of novel caudal hindbrain genes reveals different regulatory logic for gene expression in rhombomere 4 versus 5/6 in embryonic zebrafish

ABSTRACT: Analysis of novel caudal hindbrain genes reveals different regulatory logic for gene expression in rhombomere 4 versus 5/6 in embryonic zebrafish

PROVIDER: PRJNA451178 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR7041870.fastq.gz	Fastqsanger.gz
	SRR7041871.fastq.gz	Fastqsanger.gz
	SRR7041872.fastq.gz	Fastqsanger.gz
	SRR7041873.fastq.gz	Fastqsanger.gz
	SRR7041784.fastq.gz	Fastqsanger.gz

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scMultiome analysis identifies embryonic hindbrain progenitors with mixed rhombomere identities

Project description:Rhombomeres serve to position neural progenitors in the embryonic hindbrain, thereby ensuring appropriate neural circuit formation, but the molecular identities of individual rhombomeres and the mechanism whereby they form have not been fully established. Here we apply scMultiome analysis in zebrafish to molecularly resolve all rhombomeres for the first time. We find that rhombomeres become molecularly distinct between 10hpf (end of gastrulation) and 13hpf (early segmentation). While the mature hindbrain consists of alternating odd- versus even-type rhombomeres, our scMultiome analyses do not detect extensive odd versus even characteristics in the early hindbrain. Instead, we find that each rhombomere displays a unique gene expression and chromatin profile. Prior to the appearance of distinct rhombomeres, we detect three hindbrain progenitor clusters (PHPDs) that correlate with the earliest visually observed segments in the hindbrain primordium and that represent prospective rhombomere r2/r3 (possibly including r1), r4 and r5/r6, respectively. We further find that the PHPDs form in response to Fgf and RA morphogens and that individual PHPD cells co-express markers of multiple mature rhombomeres. We propose that the PHPDs contain mixed-identity progenitors and that their subdivision into individual mature rhombomeres requires resolution of these mixed-identity cell states.

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Generation of caudal-type serotonin neurons and hindbrain fate organoids from hPSCs

Project description:Serotonin (5-HT) neurons, the major components of the raphe nuclei, arise from ventral hindbrain progenitors. Based on the anatomical location and axonal projection, 5-HT neurons are coarsely divided into rostral and caudal groups. Here, we propose a novel strategy to generate hindbrain 5-HT neurons from human pluripotent stem cells (hPSCs), which involves the formation of ventral-type neural progenitor cells (NPCs) and stimulation of the hindbrain 5-HT neural development. A caudalizing agent, retinoid acid (RA), was used to direct the cells into the hindbrain cell fate. Approximately 30-40% of hPSCs successfully developed into 5-HT-expressing neurons using our protocol, with the majority acquiring a caudal rhombomere identity (r5-8). We further modified our monolayer differentiation system to generate 5-HT neuron-enriched hindbrain-like organoids. We have also suggested downstream applications of our 5-HT monolayer and organoid cultures to study neuronal response to gut microbiota. Our methodology could become a powerful tool for future studies related to 5-HT neurotransmission.

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Analysis of novel caudal hindbrain genes reveals different regulatory logic for gene expression in rhombomere 4 versus 5/6 in embryonic zebrafish.

Project description: Not available

| S-EPMC6020313 | biostudies-literature

scMultiome analysis identifies embryonic hindbrain progenitors with mixed rhombomere identities

Project description:scMultiome analysis identifies embryonic hindbrain progenitors with mixed rhombomere identities

| PRJNA926672 | ENA

Hoxb1 mutant mRNA levels in rhombomere 4 at E10.5

2006-08-28 | GSE5126 | GEO

Hoxb1 gene expressing Hox-A1 protein: Altered transcriptional profile in rhombomere 4 at E10.5

Project description:This study analyzed mRNA profiles in rhombomere 4 of E10.5 mouse knock-in embryos expressing either normal endogenous Hox-B1 protein or the paralogous Hox-A1 protein from the Hoxb1 locus. The Hox-A1 protein was found to be detectably less efficacious than Hox-B1 in promoting neurogenesis in the basal plate of rhombomere 4 and its transcriptional profile shared several similarities with the Hoxb1 mutant. Keywords: gene swap, knock-in, hindbrain development, rhombomere 4

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Generation of caudal-type serotonin neurons and hindbrain fate organoids from hPSCs

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Analysis of novel caudal hindbrain genes reveals different regulatory logic for gene expression in rhombomere 4 versus 5/6 in embryonic zebrafish

Project description:This SuperSeries is composed of the SubSeries listed below.

2018-07-15 | GSE113437 | GEO

Transcription profiling of mouse Hoxb1 mutant mRNA levels in rhombomere 4 at E10.5

Project description:Hoxb1 is required for proper specification of rhombomere 4 and the facial motor neurons. This study analyzed gene expression in the corresponding hindbrain segment of E10.5 mutant embryos. Several genetic pathways were found altered, including transcription factors such as Phox2b, Gata3, Nkx2-2 and Nkx6-1. Experiment Overall Design: Each of the three mutant and control samples was an independent biological replicate. Pools of r4 segments from multiple embryos were snap frozen on dry ice and stored at -80ÂºC. Total RNA was isolated, processed with standard Affymetrix protocols and hybridized to GeneChip Mouse Expression Sets 430A.

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