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:Neural crest cells are multipotent cells that delaminate from the neuroepithelium, migrating throughout the embryo. Aberrant migration causes developmental defects. Animal models are improving our understanding of neural crest anomalies, but in vivo migration behaviours are poorly understood. Here, we demonstrate that murine neural crest cells display actin-based lamellipodia and filopodia in vivo. Using neural crest-specific knockouts or inhibitors, we show that the serine-threonine kinase Glycogen Synthase Kinase-3 (GSK3), and the cytoskeletal regulator Lamellipodin (Lpd), are required for lamellipodia formation whilst preventing focal adhesion maturation. Lpd is a novel substrate of GSK3 and phosphorylation of Lpd favours interactions with the Scar/WAVE complex (lamellipodia formation) at the expense of VASP and Mena interactions (adhesion maturation and filopodia formation). This improved understanding of cytoskeletal regulation in mammalian neural crest migration has general implications for neural crest anomalies and cancer.
Project description:To elucidate the molecular features of craniofacial versus trunk neural crest cells (NCCs), we utilized P0-Cre/Floxed-EGFP mice that specifically label NCCs (Yamauchi et al., 1999 (PMID 10419695)). Craniofacial and trunk regions were isolated from P0-Cre/Floxed-EGFP mouse embryos at embryonic day E12.5, and dissociated cells were analyzed by flow cytometory in regard to the intensity of EGFP.
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 anterior and posterior cranial regions of E9.25 mouse embryos.
Project description:To elucidate the molecular features of craniofacial versus trunk neural crest cells (NCCs), we utilized P0-Cre/Floxed-EGFP mice that specifically label NCCs (Yamauchi et al., 1999 (PMID 10419695)). Craniofacial and trunk regions were isolated from P0-Cre/Floxed-EGFP mouse embryos at embryonic day E12.5, and dissociated cells were analyzed by flow cytometory in regard to the intensity of EGFP. In this study, we performed at least duplicate experiments for each of the four groups (Craniofacial EGFP+, Trunk EGFP+, Craniofacial EGFP-, Trunk EGFP-). Total of 9 samples.
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.