Project description:The genetic and developmental mechanisms that control the decision between scale and feather growth â two profoundly different epidermal appendages, and an important developmental shift in the evolution of birds from their dinosaurian ancestors â remain poorly understood. Domestic pigeons display dramatic variation in foot epidermal appendages within a single species, and classical studies suggest that a small number of genes control much of this variation; thus pigeons provide a tractable model to understand skin appendage specification and variation. Here we show that feathered feet in pigeons are the consequence of a partial transformation of limb-type identity mediated by cis-regulatory changes in the hindlimb-specific transcription factor Pitx1 and forelimb-specific transcription factor Tbx5. We also demonstrate that ectopic hindlimb expression of Tbx5 is associated with the development of foot feathers in domestic chickens, suggesting that similar developmental mechanisms underlie phenotypic convergence in avian lineages that diverged over 100 MYA. These results show how qualitative and quantitative changes in expression of regional patterning genes can generate localized changes in organ fate and morphology, and provide a viable molecular mechanism for the evolution of hindlimb scale and feather distribution in dromaeosaurs. Examination of H3K27ac status in embryonic limb buds from two domestic pigeon breeds, racing homer and Indian fantail
Project description:Domestic rock pigeons (Columba livia) homozygous for either of two “recessive red” mutations, which are partially-overlapping deletions causing downregulation of Sox10, display brilliant red colors instead of blue/black feathers. Sox10 encodes a transcription factor important for melanocyte differentiation and function, but the precise role that it plays in promoting eumelanin over pheomelanin pigment production in pigeons are unknown. In this study, we perform ChIPseq for SOX10, H3K27ac, and H3K27me3 to better understand the genome occupancy of SOX10 in avian melanocytes.
Project description:Ulcerative colitis is a chronic inflammatory disorder for which a definitive cure is still missing. This is characterized by an overwhelming inflammatory milieu in the colonic tract where a composite set of immune and non-immune cells orchestrate its pathogenesis. Over the last years, a growing body of evidence has been pinpointing gut virome dysbiosis as underlying its progression. Nonetheless, its role during the early phases of chronic inflammation is far from being fully defined. Here we show the gut virome-associated Hepatitis B virus protein X, most likely acquired after an event of zoonotic spillover, to be associated with the early stages of ulcerative colitis and to induce colonic inflammation in mice. It acts as a transcriptional regulator in epithelial cells, provoking barrier leakage and altering mucosal immunity at the level of both innate and adaptive immunity. This study paves the way to the comprehension of the aetiopathogenesis of intestinal inflammation and encourages further investigations of the virome as a trigger also in other scenarios. Moreover, it provides a brand-new standpoint that looks at the virome as a target for tailored treatments, blocking the early phases of chronic inflammation and possibly leading to better disease management.
Project description:The genetic and developmental mechanisms that control the decision between scale and feather growth – two profoundly different epidermal appendages, and an important developmental shift in the evolution of birds from their dinosaurian ancestors – remain poorly understood. Domestic pigeons display dramatic variation in foot epidermal appendages within a single species, and classical studies suggest that a small number of genes control much of this variation; thus pigeons provide a tractable model to understand skin appendage specification and variation. Here we show that feathered feet in pigeons are the consequence of a partial transformation of limb-type identity mediated by cis-regulatory changes in the hindlimb-specific transcription factor Pitx1 and forelimb-specific transcription factor Tbx5. We also demonstrate that ectopic hindlimb expression of Tbx5 is associated with the development of foot feathers in domestic chickens, suggesting that similar developmental mechanisms underlie phenotypic convergence in avian lineages that diverged over 100 MYA. These results show how qualitative and quantitative changes in expression of regional patterning genes can generate localized changes in organ fate and morphology, and provide a viable molecular mechanism for the evolution of hindlimb scale and feather distribution in dromaeosaurs.
Project description:In feather-footed pigeons, mutant alleles of PITX1 and TBX5 drive the partial redeployment of an evolutionarily conserved forelimb genetic program in the hindlimb.
Project description:Necrotizing enterocolitis (NEC) is a severe intestinal disorder connected to a gut microbiota dysbiosis. Approximately 7-8% of very low birth weight (VLBW) infants are diagnosed with NEC with mortality rates reaching 20-50%. Fecal virome transfer (FVT) is an approach where the bacteria-free fecal fraction from a healthy donor is administered to a patient with a GM dysbiosis. FVT contains e.g. bacteriophages, eukaryotic viruses, and metabolites. Oral administered FVT from healthy milk-fed term pigs shows promising potential in preventing NEC in the preterm piglet model. However, efficacy and safety are inconsistent between experiments. In the current study, we aim to explore methods of creating reproducible FVT-like treatments and test if these act preventive against NEC and possess minimal side effects in the preterm piglet model. Using cesarean-delivered, formula-fed preterm pigs, we compare the NEC preventive effect of native donor fecal virome (nFV) with: 1) a defined bacteriophage cocktail targeting NEC-associated bacteria; and 2) a chemostat fecal virome propagation with lactose as the major carbohydrate source (cFV), and 3) chemostat fecal virome propagation with lactose and milk oligosaccharides (cFV-OS). All methods will be compared to control treatment with SM buffer (SM).