Project description:We apply developmental and single cell gene expression analysis to fetal skin of domestic cats, together with genetic characterization of Mendelian color variation, to identify when, where, and how, during fetal development, felid color patterns are established. Prior to the appearance of hair follicle placodes, we identify changes in epidermal thickness that represent a signature of color pattern establishment, and that are preceded by a pre-pattern of gene expression in which the secreted Wnt inhibitor encoded by Dickkopf 4 (Dkk4) plays a central role. We also demonstrate that mutations in Dkk4 underlie the Ticked pattern mutation in cats. Our results bring molecular understanding to how the leopard got its spots, suggest that similar mechanisms underlie periodic color pattern and periodic hair follicle spacing, and provide a genomic framework to explore natural selection for diverse pattern types in wild felids.
Project description:Intricate color patterns are a defining aspect of morphological diversity in the Felidae. We applied morphological and single-cell gene expression analysis to fetal skin of domestic cats to identify when, where, and how, during fetal development, felid color patterns are established. Early in development, we identify stripe-like alterations in epidermal thickness preceded by a gene expression pre-pattern. The secreted Wnt inhibitor encoded by Dickkopf 4 plays a central role in this process, and is mutated in cats with the Ticked pattern type. Our results bring molecular understanding to how the leopard got its spots, suggest that similar mechanisms underlie periodic color pattern and periodic hair follicle spacing, and identify targets for diverse pattern variation in other mammals.
Project description:Many animals exhibit typical color patterns that have been linked to key adaptive functions, yet the developmental mechanisms establishing these crucial designs remain unclear. Here, we surveyed color distribution in the plumage across a large number of passerine finches. Despite extreme apparent pattern diversity, we identified a small set of conserved color regions whose combinatory association can explain all observed patterns. We found these domains are instructed by signals from embryonic somites and lateral plate mesoderm, and through profiling and comparative analyses, produced a molecular map marking putative color domains in the developing skin. This revealed cryptic pre-patterning common to differently colored species, uncovering a simple molecular landscape underlying extensive color pattern variation.
Project description:MicroRNAs negatively regulate gene expression and may serve as biomarkers for human cardiomyopathy. In the domestic cat, hypertrophic cardiomyopathy (HCM) represents the most common primary cardiomyopathy. In humans, the etiology of HCM is linked to mutations in genes of contractile muscle proteins, while in cats a clear proof for causal mutations is missing. The etiology of feline HCM is uncertain. Diagnosis is made by heart ultrasound examination and measuring the serum level of N-terminal pro B-type natriuretic peptide. The purpose of this study was to investigate whether microRNA profiles in the serum of cats with HCM are different from the profiles of healthy cats and whether specific miRNAs can be detected to serve as potential biomarkers for feline HCM or may help in understanding the etiology of this disease Blood was drawn from two groups of cats: 12 healthy cats and 11 cats suffering from hypertrophic cardiomyopathy. After clotting, samples were centrifuged and total mRNA was extracted from serum. These 23 serum samples were analyzed and the groups were compared
Project description:BACKGROUND: MicroRNAs negatively regulate gene expression and play a pivotal role in the pathogenesis of human type 2 diabetes mellitus (T2DM). As the domestic cat presents a spontaneous animal model for human T2DM, the purpose of this study was to investigate whether microRNAs are detectable in feline serum and whether microRNA expression profiles differ between healthy and diabetic cats. METHODS: Total RNA was extracted from 400 M-BM-5l serum of healthy lean (HL) and newly diagnosed diabetic (D) cats. MicroRNA microarrays representing 1079 distinct mouse miRNA targets were used to measure miRNA expression in samples from eight HL and eight D cats. RESULTS: By microarray, 227 distinct microRNAs were identified. Nineteen miRNAs were differentially expressed in diabetic cats, but only two reached statistical significance after correction for multiple comparisons. In qRT-PCR, miR-122* was found to be upregulated in diabetic cats more than 40-fold compared to HL cats, while miR-193b was upregulated about 10-fold. MiR-483* showed a 6- fold increase in diabetic cats compared to HL cats. CONCLUSIONS: Small volumes of serum samples yield sufficient material to detect altered microRNA expression profiles in diabetic cats. The domestic cat may be considered a useful animal model for studying miRNAs involved in human T2DM. Blood was drawn from two groups of cats: 8 healthy cats and 8 cats suffering from diabetes. After clotting, samples were centrifuged and total mRNA was extracted from serum. These 16 serum samples were analyzed and the groups were compared. Due to technical problems during hybridization (leaking chamber), sample 1_4_B (Serum_diabetic_8) was not included into analysis.
Project description:We investigated gene expression levels in Heliconius erato butterflies with divergent wing patterns across a 656KB genomic interval linked to the red color pattern wing polymorphism. This included comparison of expression between two H. erato color pattern populations (H. e. petiverana and a H.e. etylus x H. himera hybrid) across three sections of the forewing that differed in pigmentation (the basal, mid, and distal wing sections) and five different stages of pupal development (Day 1, 3, 5 pupae and ommochrome and melanin pigmentation stages). These results allowed us to determine whether certain genes in this interval were differentially expressed between the wing pattern elements, and, therefore, potentially responsible for adaptive color pattern variation in these butterflies.
Project description:We know very little about the genetic basis for color and color-pattern in squamate reptiles - a group with over 10,000 species of snakes and lizards. Using transcriptomic comparisons between orange, yellow and white tissues from an anole lizard, we identified 6 color and 7 color-pattern candidate genes in squamates that are conserved across other vertebrates like mammals, birds or fish. Among color genes, we identified the first candidate gene for converting yellow xanthophylls to red ketocarotenoids in squamates, and a sex-linked protein that transports carotenoids from the bloodstream into the pigment cells. A new model for the genetics of coloration in squamates informed by our data suggests that the genes and associated pathways underlying both color and color-pattern are broadly conserved across vertebrates.
Project description:BACKGROUND: MicroRNAs negatively regulate gene expression and play a pivotal role in the pathogenesis of human type 2 diabetes mellitus (T2DM). As the domestic cat presents a spontaneous animal model for human T2DM, the purpose of this study was to investigate whether microRNAs are detectable in feline serum and whether microRNA expression profiles differ between healthy and diabetic cats. METHODS: Total RNA was extracted from 400 µl serum of healthy lean (HL) and newly diagnosed diabetic (D) cats. MicroRNA microarrays representing 1079 distinct mouse miRNA targets were used to measure miRNA expression in samples from eight HL and eight D cats. RESULTS: By microarray, 227 distinct microRNAs were identified. Nineteen miRNAs were differentially expressed in diabetic cats, but only two reached statistical significance after correction for multiple comparisons. In qRT-PCR, miR-122* was found to be upregulated in diabetic cats more than 40-fold compared to HL cats, while miR-193b was upregulated about 10-fold. MiR-483* showed a 6- fold increase in diabetic cats compared to HL cats. CONCLUSIONS: Small volumes of serum samples yield sufficient material to detect altered microRNA expression profiles in diabetic cats. The domestic cat may be considered a useful animal model for studying miRNAs involved in human T2DM.
Project description:MicroRNAs negatively regulate gene expression and may serve as biomarkers for human cardiomyopathy. In the domestic cat, hypertrophic cardiomyopathy (HCM) represents the most common primary cardiomyopathy. In humans, the etiology of HCM is linked to mutations in genes of contractile muscle proteins, while in cats a clear proof for causal mutations is missing. The etiology of feline HCM is uncertain. Diagnosis is made by heart ultrasound examination and measuring the serum level of N-terminal pro B-type natriuretic peptide. The purpose of this study was to investigate whether microRNA profiles in the serum of cats with HCM are different from the profiles of healthy cats and whether specific miRNAs can be detected to serve as potential biomarkers for feline HCM or may help in understanding the etiology of this disease