Project description:We demonstrate for the first time that the extracellular matrix glycoprotein Tenascin-C regulates the expression of key patterning genes during late embryonic spinal cord development, leading to a timely maturation of gliogenic neural precursor cells. We first show that Tenascin-C is expressed by gliogenic neural precursor cells during late embryonic development. The loss of Tenascin-C leads to a sustained generation and delayed migration of Fibroblast growth factor receptor 3 expressing immature astrocytes in vivo. Furthermore, we could demonstrate an upregulation of Nk2 transcription factor related locus 2 (Nkx2.2) and its downstream target Sulfatase 1 in vivo. A dorsal expansion of Nkx2.2-positive cells within the ventral spinal cord indicates a potential progenitor cell domain shift. Moreover, Sulfatase 1 is known to regulate growth factor signalling by cleaving sulphate residues from heparan sulphate proteoglycans. Consistent with this possibility we observed changes in both Fibroblast growth factor 2 and Epidermal growth factor responsiveness of spinal cord neural precursor cells. Taken together our data clearly show that Tenascin-C promotes the astroglial lineage progression during spinal cord development.
Project description:Chromosomes and genes are non-randomly arranged within the mammalian cell nucleus. Clustering of genes is of great significance in transcriptional regulation. However, the relevance of gene clustering in their expression during differentiation of neural precursor cells (NPCs) into astrocytes remains unclear. We performed a genome-wide enhanced circular chromosomal conformation capture (e4C) to screen genes associated with an astrocyte-specific gene, glial fibrillary acidic protein (Gfap), during astrocyte differentiation. We identified 13 genes that were specifically associated with Gfap and expressed in NPC-derived astrocytes. These results provide evidence for functional significance of gene clustering in transcriptional regulation during NPCs differentiation. comparison of NPCs vs LIF+ vs LIF- cells.
Project description:We demonstrate for the first time that the extracellular matrix glycoprotein Tenascin-C regulates the expression of key patterning genes during late embryonic spinal cord development, leading to a timely maturation of gliogenic neural precursor cells. We first show that Tenascin-C is expressed by gliogenic neural precursor cells during late embryonic development. The loss of Tenascin-C leads to a sustained generation and delayed migration of Fibroblast growth factor receptor 3 expressing immature astrocytes in vivo. Furthermore, we could demonstrate an upregulation of Nk2 transcription factor related locus 2 (Nkx2.2) and its downstream target Sulfatase 1 in vivo. A dorsal expansion of Nkx2.2-positive cells within the ventral spinal cord indicates a potential progenitor cell domain shift. Moreover, Sulfatase 1 is known to regulate growth factor signalling by cleaving sulphate residues from heparan sulphate proteoglycans. Consistent with this possibility we observed changes in both Fibroblast growth factor 2 and Epidermal growth factor responsiveness of spinal cord neural precursor cells. Taken together our data clearly show that Tenascin-C promotes the astroglial lineage progression during spinal cord development. in total 6 probes: 3 replica of TNC_wt and 3 replica of TNC_ko
Project description:Neural crest cells are migratory progenitor cells that contribute to nearly all tissues and organs throughout the body. Their formation, migration and differentiation are regulated by a multitude of signaling pathways, that when disrupted can lead to disorders termed neurocristopathies. While work in avian and amphibian species has revealed essential factors governing the specification and induction of neural crest cells during gastrulation and neurulation in non-mammalian species, their functions do not appear to be conserved in mice, leaving major gaps in our understanding of neural crest cell formation in mammals. Here we describe Germ Cell Nuclear Factor (GCNF/Nr6a1), an orphan nuclear receptor, as a critical regulator of neural crest cell formation in mice. Gcnf null mutant mice, exhibit a major disruption of neural crest cell formation. The purpose of this experiment is to examine gene expression changes in response to Gcnf mutation in E9.0 mouse embryos.
Project description:Introgressed variants from other species can be an important source of genetic variation because they may arise rapidly, can include multiple mutations on a single haplotype, and have often been pretested by selection in the species of origin. Although introgressed alleles are generally deleterious, several studies have reported introgression as the source of adaptive alleles-including the rodenticide-resistant variant of Vkorc1 that introgressed from Mus spretus into European populations of Mus musculus domesticus. Here, we conducted bidirectional genome scans to characterize introgressed regions into one wild population of M. spretus from Spain and three wild populations of M. m. domesticus from France, Germany, and Iran. Despite the fact that these species show considerable intrinsic postzygotic reproductive isolation, introgression was observed in all individuals, including in the M. musculus reference genome (GRCm38). Mus spretus individuals had a greater proportion of introgression compared with M. m. domesticus, and within M. m. domesticus, the proportion of introgression decreased with geographic distance from the area of sympatry. Introgression was observed on all autosomes for both species, but not on the X-chromosome in M. m. domesticus, consistent with known X-linked hybrid sterility and inviability genes that have been mapped to the M. spretus X-chromosome. Tract lengths were generally short with a few outliers of up to 2.7 Mb. Interestingly, the longest introgressed tracts were in olfactory receptor regions, and introgressed tracts were significantly enriched for olfactory receptor genes in both species, suggesting that introgression may be a source of functional novelty even between species with high barriers to gene flow.