Dataset Information

Detailed expression analysis of regulatory genes in the early developing human neural tube.

ABSTRACT: Studies in model organisms constitute the basis of our understanding of the principal molecular mechanisms of cell fate determination in the developing central nervous system. Considering the emergent applications in stem cell-based regenerative medicine, it is important to demonstrate conservation of subtype specific gene expression programs in human as compared to model vertebrates. We have examined the expression patterns of key regulatory genes in neural progenitor cells and their neuronal and glial descendants in the developing human spinal cord, hindbrain, and midbrain, and compared these with developing mouse and chicken embryos. As anticipated, gene expression patterns are highly conserved between these vertebrate species, but there are also features that appear unique to human development. In particular, we find that neither tyrosine hydroxylase nor Nurr1 are specific markers for mesencephalic dopamine neurons, as these genes also are expressed in other neuronal subtypes in the human ventral midbrain and in human embryonic stem cell cultures directed to differentiate towards a ventral mesencephalic identity. Moreover, somatic motor neurons in the ventral spinal cord appear to be produced by two molecularly distinct ventral progenitor populations in the human, raising the possibility that the acquisition of unique ventral progenitor identities may have contributed to the emergence of neural subtypes in higher vertebrates.

SUBMITTER: Marklund U

PROVIDER: S-EPMC3870486 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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Detailed expression analysis of regulatory genes in the early developing human neural tube.

Marklund Ulrika U Alekseenko Zhanna Z Andersson Elisabet E Falci Scott S Westgren Magnus M Perlmann Thomas T Graham Anthony A Sundström Erik E Ericson Johan J

Stem cells and development 20131008 1

Studies in model organisms constitute the basis of our understanding of the principal molecular mechanisms of cell fate determination in the developing central nervous system. Considering the emergent applications in stem cell-based regenerative medicine, it is important to demonstrate conservation of subtype specific gene expression programs in human as compared to model vertebrates. We have examined the expression patterns of key regulatory genes in neural progenitor cells and their neuronal a ...[more]

PMID: 24007338

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Project description:At an incidence of approximately 1/1000 births, neural tube defects (NTDs) comprise one of the most common and devastating congenital disorders. In an attempt to enhance and expand our understanding of neural tube closure, we undertook a high-throughput gene expression analysis of the neural tube as it was forming in the mouse embryo. Open and closed sections of the developing neural tube were micro-dissected from mouse embryos, and hybridized to Affymetrix mouse expression arrays. Clustering of genes differentially regulated in open and closed sections of the developing neural tube highlighted molecular processes previously recognized to be involved in neural tube closure and neurogenesis. Analysis of the genes in these categories identified potential candidates underlying neural tube closure. In addition, we identified approximately 25 novel genes, of unknown function, that were significantly up-regulated in the closed neural tube. Based on their expression patterns in the developing neural tube, five novel genes are proposed as interesting candidates for involvement in neurogenesis. The high-throughput expression analysis of the neural tube as it forms allows for better characterization of pathways involved in neural tube closure and neurogenesis, and hopefully will strengthen the foundation for further research along the pathways dictating neural tube development. Embryos were dissected at days E8.5 and E9.5, and the neuroepithelium/ neural tube were mechanically detached from underlying tissues, and then separated into two regions: 1) M-bM-^@M-^\open neuroepitheliumM-bM-^@M-^]: neuroepithelial tissue caudal to the open/closed junction, and 2) M-bM-^@M-^\closed neural tubeM-bM-^@M-^], extending from a somiteM-bM-^@M-^Ys breadth rostral to the open/closed junction, up to the level of the fifth- or sixth-to-last somite. Samples consisted of biological triplicates of RNA extract from the above tissues (pooled by litter, and representing a total of 111 embryos): E8.5 open neuroepithelium, E8.5 closed neural tube, E9.5 open neuroepithelium, and E9.5 closed neural tube. Thus, a total of 12 samples (representing 111 embryos) were hybridized to the GeneChip Mouse Genome 430 2.0 Array (Affymetrix Inc., Santa Clara, CA, USA). One of the samples (06, closed E8.5) deviated significantly from the others in quality assessment and was therefore removed from subsequent analysis and not submitted to GEO.

Dataset Information

Detailed expression analysis of regulatory genes in the early developing human neural tube.

Publications

Detailed expression analysis of regulatory genes in the early developing human neural tube.

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