RBM19 is essential for preimplantation development in the mouse

Homozygous mutant embryos failed to develop beyond the morula stage, showing defective nucleologenesis, activation of apoptosis, and upregulation of P53 target genes. A unique feature of RBM19 is its localization to the cytoplasm in morula stage-embryos, whereas most other nucleolar proteins are localized to the nucleolar precursor body (NPB). The nucleoli in the Rbm19 mutant embryos remain immature, yet they can carry out rRNA synthesis. The timing of developmental arrest occurs after expression of the inner cell mass markers OCT3/4 and NANOG, but prior to the specification of trophectoderm as reflected by CDX2 expression.The data indicate that RBM19 is essential for preimplantation development, highlighting the importance of de novo nucleologenesis during this critical developmental stage.During early embryogenesis, the zygotic nucleolus assembles from a ground state following the disassembly of the maternal nucleolus after pronuclear fusion [1]. "De novo" nucleologenesis begins in the mouse at the end of the 2nd cell cycle with the initiation of ribosomal RNA transcription. An early morphological intermediate of the reforming nucleolus is the nucleolus precursor body (NPB) [2]. The NPB can be detected through the morula stage, after which it progressively adopts the classic tripartite morphology as seen in the blastocyst and thereafter. Ribosomal RNA transcription begins on the surface of the sphere, where the nucleolar organizing regions (NORs) of the genome are located [3]. In contrast to somatic (i.e. post-mitotic) nucleologenesis, the mechanism and role in development of de novo nucleologenesis are not well understood.The role of nucleolar proteins during early mouse development has been investigated by gene targeting in the mouse. In virtually all cases, genetic ablation of protein function results in developmental arrest prior to birth, but at stages that might not be predictable a priori based on the encoded protein's function. For example, in embryos muta