Prenatal development of mammalian fetuses relies on an important organ known as the placenta. Despite its critical function in gas exchange, nutrient transport and immunity at the maternal-fetal interface, the placenta is the most morphologically diverse organ in mammals, with at least five different forms. One of these forms include the zonary placenta, which has a unique belt-like structure that wraps around the fetus. The zonary placenta consists of multiple tissues in three major zones: the transfer zone, the pigmented zone and the allantochorion. The function of each of these zones remains poorly understood. Female dogs have two X chromosomes and males only have one, resulting an unequal dose of X-linked genes. Dosage compensation is achieved by inactivating one X chromosome in females through a process called X chromosome inactivation. Different strategies, including random and imprinted X chromosome inactivation, are observed in mammalian placentae. The mechanism of X chromosome inactivation in canine placenta is unknown. To fill in these gaps, we propose to characterize gene expression profiles and regulation of X chromosome inactivation in different canine placental tissues. This proposed research will lead to comprehensive understanding of regulated gene expression and a comparative analysis of dosage compensation across different types of animals.
The goal of this research is to understand the gene expression and epigenetic control of X chromosome dosage compensation in the zonary placenta. The mammalian placenta is a key evolutionary innovation that dramatically improves the reproductive success through in utero development of the embryos. Despite its critical function, placenta is the most morphologically diverse organ with five major placentation forms. Zonary placenta is observed in carnivores including companion animals such as cats and dogs. The band shaped placenta encircles the fetus with three distinct zones: the transfer zone, the pigmented zone and the allantochorion. Their functions and transcriptome profiles are still poorly understood. In therian mammals, females and males have unequal dose of X-linked genes, and this is solved by a mechanism called dosage compensation (DC). In somatic tissues of eutherian mammals, DC is achieved by random X chromosome inactivation (XCI) in females, in which one of the two X chromosomes is inactivated and the choice is random. In the extraembryonic tissues that give rise to placenta, imprinted XCI was observed in rodents, in which it is always the paternal X that is inactivated. The XCI status remains to be characterized in zonary placenta. This project will achieve the following objectives: 1) Characterize the full-length transcriptomes and functional enrichment of gene networks in the transfer zone, pigmented zone and allantochorion of the canine placenta, 2) Investigate the form, status, escaping profile and epigenetic regulation of XCI in the zonary placenta. This proposed research will lead to comprehensive understanding of the profile and epigenetic regulation of XCI in zonary placenta through single-cell RNA sequencing, which opens the door to comparative phylogenomic analysis of dosage compensation.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
