Embryonic development is a complex and dynamic process that involves spatiotemporal expression of genes in a highly coordinated manner. Multiple levels of nuclear architecture maintain the fidelity of gene expression programme. One of the components of nuclear architecture, which is believed to play an important role in regulation of gene expression, is the nuclear matrix (NuMat). Many studies over the past few years have tried to analyse the components of this non-chromatin scaffolding of the nucleus and have provided evidences of its structural and functional complexity. However, the relationship of NuMat with the process of embryonic development still remains poorly understood. Here, we report a comparative analysis of the NuMat proteomes of early and late stage Drosophila melanogaster embryos and show that 65% of the NuMat proteome is dynamic during development. Our study establishes links between the dynamics of nuclear architecture and embryonic development and provides tools to further understand the process such as cellular differentiation in the context of higher-order nuclear organization.