Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Sip1 in cortical interneuron migration

ABSTRACT: We sequenced mRNA from 6 samples of FACsorted telencephalons from E14.5 Sip1|Nkx2-1 knockout and WT|Nkx2-1 control mouse embryos to find differentially expressed genes in the absence of the transcription factor Sip1. Examination of mRNA levels in 3 control and 3 Sip1|Nkx2-1 knockout samples

ORGANISM(S): Mus musculus

SUBMITTER: Bram Van de Sande

PROVIDER: E-GEOD-35616 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Directed migration of cortical interneurons depends on the cell-autonomous action of Sip1.

van den Berghe Veronique V Stappers Elke E Vandesande Bram B Dimidschstein Jordane J Kroes Roel R Francis Annick A Conidi Andrea A Lesage Flore F Dries Ruben R Cazzola Silvia S Berx Geert G Kessaris Nicoletta N Vanderhaeghen Pierre P van Ijcken Wilfred W Grosveld Frank G FG Goossens Steven S Haigh Jody J JJ Fishell Gord G Goffinet André A Aerts Stein S Huylebroeck Danny D Seuntjens Eve E

Neuron 20130101 1

GABAergic interneurons mainly originate in the medial ganglionic eminence (MGE) of the embryonic ventral telencephalon (VT) and migrate tangentially to the cortex, guided by membrane-bound and secreted factors. We found that Sip1 (Zfhx1b, Zeb2), a transcription factor enriched in migrating cortical interneurons, is required for their proper differentiation and correct guidance. The majority of Sip1 knockout interneurons fail to migrate to the neocortex and stall in the VT. RNA sequencing reveals ...[more]

PMID: 23312517

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Project description:Background: Mutations in the cone-rod-homeobox protein CRX are typically associated with dominant blinding retinopathies with variable age of onset and severity. Five well-characterized mouse models carrying different Crx mutations show a wide range of disease phenotypes. To determine if the phenotype variability correlates with distinct changes in CRX target gene expression, we perform RNA-seq analyses on three of these models and compare the results with published data. Results: Despite dramatic phenotypic differences between the three models tested, graded expression changes in shared sets of genes are detected. Phenotype severity correlates with the down-regulation of genes encoding key rod and cone phototransduction proteins. Interestingly, in increasingly severe mouse models, the transcription of many rod-enriched genes decreases decrementally, whereas that of cone-enriched genes increases incrementally. Unlike down-regulated genes, which show a high degree of CRX binding and dynamic epigenetic profiles in normal retinas, the up-regulated cone-enriched genes do not correlate with direct activity of CRX, but instead likely reflect a change in rod cell-fate integrity. Furthermore, these analyses describe the impact of minor gene expression changes on the phenotype, as two mutants showed marginally distinguishable expression patterns but huge phenotypic differences, including distinct mechanisms of retinal degeneration. Conclusions: Our results implicate a threshold effect of gene expression level on photoreceptor function and survival, highlight the importance of CRX in photoreceptor subtype development and maintenance, and provide a molecular basis for phenotype variability in CRX-associated retinopathies. All genotypes were analyzed in triplicate. Heterozygous and homozygous mutants were all sequenced at P10, the control for which is the P10 C57BL6/J data. Heterozygous mutants were also analyzed at P21, the control for which is the P21 C57BL6/J data.

Dataset Information

Sip1 in cortical interneuron migration

Publications

Directed migration of cortical interneurons depends on the cell-autonomous action of Sip1.

Similar Datasets

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