Coordination and function of nuclear lamina and nuclear pore compartmentalisation in genome organisation during early mouse development
The packaging of the chromosomes in the cell nucleus while retaining fundamental DNA-based activities such as transcription and replication represents an enormous organisation challenge. Indeed, the way in which the DNA is folder into the 3 dimensions of the cell nucleus can affect gene expression and thus cellular identity. How nuclear organisation is first established after fertilisation in mammals is largely unknown. Following fertilisation, a period of intense chromatin remodeling and epigenetic reprogramming of the two parental genomes occurs. Such remodeling is necessary to start a developmental programme capable of forming a new organism. Several nuclear landmarks can provide positional cues to the genome and thus are key contributors to genome organization. Amongst them, the nucleolus, the nuclear lamina and speckles organise the chromatin into functionally relevant domains and have been extensively studied. In addition, a role for the nuclear pore in nuclear organization has been suggested and studies in somatic cells in culture have revealed a role for components of the nuclear pore in gene regulation. However, how the nuclear pores first assemble at the beginning of development or the components that characterise embryonic nuclear pores are largely unknown. In addition, the genomic regions that interact with the nuclear pore as the embryo develops and whether such association is functionally relevant for key developmental landmarks such as zygotic genome activation and cell fate allocation has not been investigated. This project thus aims to i) characterize the components and cellular architecture of the nuclear pore at the beginning of mammalian development, ii) to map genome interactions with nuclear pore components during reprogramming as development proceeds, and iii) to determine the functional role of nuclear pore components in the establishment of genome topology, de novo in mammalian development. Using a combination of cell and molecular biology as well as perturbations through experimental embryology in mouse embryos, we will provide a comprehensive functional characterization of the nuclear pore and its components during early development. Altogether, our data will shed light into the organization and the molecular determinants of nuclear architecture during development.
Dr. Maria Elena Torres-Padilla,Munich
Helmholtz Zentrum München
Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH)
Institute of Epigenetics and Stem Cells (IES)