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Sox12 deletion in the mouse reveals nonreciprocal redundancy with the related Sox4 and Sox11 transcription factors.

ABSTRACT: The transcription factors Sox4 and Sox11 are important regulators of diverse developmental processes including heart, lung, pancreas, spleen, and B-cell development. Here we have studied the role of the related Sox12 as the third protein of the SoxC group both in vivo and in vitro. Despite widespread Sox12 expression during embryonic development, Sox12-deficient mice developed surprisingly normally, so that they were born alive, showed no gross phenotypic abnormalities, and were fertile in both sexes. Comparison with the related Sox4 and Sox11 revealed extensive overlap in the embryonic expression pattern but more uniform expression levels for Sox12, without sites of particularly high expression. All three Sox proteins furthermore exhibited comparable DNA-binding characteristics and functioned as transcriptional activators. Sox12 was, however, a relatively weak transactivator in comparison to Sox11. We conclude that Sox4 and Sox11 function redundantly with Sox12 and can compensate its loss during mouse development. Because of differences in expression levels and transactivation rates, however, functional compensation is not reciprocal.

SUBMITTER: Hoser M

PROVIDER: S-EPMC2493363 | biostudies-literature | 2008 Aug

REPOSITORIES: biostudies-literature

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Sox12 deletion in the mouse reveals nonreciprocal redundancy with the related Sox4 and Sox11 transcription factors.

Hoser Melanie M Potzner Michaela R MR Koch Julia M C JM Bösl Michael R MR Wegner Michael M Sock Elisabeth E

Molecular and cellular biology 20080527 15

The transcription factors Sox4 and Sox11 are important regulators of diverse developmental processes including heart, lung, pancreas, spleen, and B-cell development. Here we have studied the role of the related Sox12 as the third protein of the SoxC group both in vivo and in vitro. Despite widespread Sox12 expression during embryonic development, Sox12-deficient mice developed surprisingly normally, so that they were born alive, showed no gross phenotypic abnormalities, and were fertile in both ...[more]

PMID: 18505825

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Project description:BackgroundDevelopment of the cerebral cortex requires highly specific spatio-temporal regulation of gene expression. It is proposed that transcriptome profiling of the cerebral cortex at various developmental time points or regions will reveal candidate genes and associated molecular pathways involved in cerebral corticogenesis.ResultsSerial analysis of gene expression (SAGE) libraries were constructed from C57BL/6 mouse cerebral cortices of age embryonic day (E) 15.5, E17.5, postnatal day (P) 1.5 and 4 to 6 months. Hierarchical clustering analysis of 561 differentially expressed transcripts showed regionalized, stage-specific and co-regulated expression profiles. SAGE expression profiles of 70 differentially expressed transcripts were validated using quantitative RT-PCR assays. Ingenuity pathway analyses of validated differentially expressed transcripts demonstrated that these transcripts possess distinctive functional properties related to various stages of cerebral corticogenesis and human neurological disorders. Genomic clustering analysis of the differentially expressed transcripts identified two highly transcribed genomic loci, Sox4 and Sox11, during embryonic cerebral corticogenesis. These loci feature unusual overlapping sense and antisense transcripts with alternative polyadenylation sites and differential expression. The Sox4 and Sox11 antisense transcripts were highly expressed in the brain compared to other mouse organs and are differentially expressed in both the proliferating and differentiating neural stem/progenitor cells and P19 (embryonal carcinoma) cells.ConclusionsWe report validated gene expression profiles that have implications for understanding the associations between differentially expressed transcripts, novel targets and related disorders pertaining to cerebral corticogenesis. The study reports, for the first time, spatio-temporally regulated Sox4 and Sox11 antisense transcripts in the brain, neural stem/progenitor cells and P19 cells, suggesting they have an important role in cerebral corticogenesis and neuronal/glial cell differentiation.

Dataset Information

Sox12 deletion in the mouse reveals nonreciprocal redundancy with the related Sox4 and Sox11 transcription factors.

Publications

Sox12 deletion in the mouse reveals nonreciprocal redundancy with the related Sox4 and Sox11 transcription factors.

Similar Datasets

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