Borealin is differentially expressed in ES cells and is essential for the early development of embryonic cells

Abstract

Maintaining undifferentiated state and self-renewal ability of embryonic stem cells is a process that many genes and factors participate in. Using bioinformatics analyses and suppression subtractive hybridization we cloned a novel human gene related to the proliferation of human embryonic stem (hES) cells and its mouse homologue and identified them as being borealin. Our data demonstrated that borealin was highly expressed in undifferentiated ES cells, mouse pre-implantation embryos and the brain of 8.5-9.5 day post-coitum mouse embryos. Furthermore, following Borealin depletion by microinjecting anti-Borealin antibody into the zygotes the mouse embryos were arrested at the 2 or 4-cell stage and chromosomes could not correctly localize at the equator plane of the mitotic spindle and most cells had two or more nuclei. Taken together, these results indicate that Borealin plays a crucial role in the early mouse embryonic development.

Genome-wide microarray evidence that 8-cell human blastomeres over-express cell cycle drivers and under-express checkpoints

“…Four of the six cycling mitosis genes were over-detected on both 8-Cell and hES arrays relative to fibroblasts: CDCA8 (borealin), ESPL1 (separase), FBX05 (Emi1) and TPX2. Borealin is a chromosomal passenger protein required for stability of the bipolar mitotic spindle [37] and recently reported to be essential for cleavage from the 2-cell to 4-cell stage of mouse embryos [38]; separase cleaves cohesin to allow the separation of sister chromatids [39] and cleaves the linker between mother and daughter centrioles to license centriole duplication [40]; Emi1 represses APC/C cdh1 in G2 [36], thus blocking the degradation of Cyclin A, -B and geminin, and allowing both the formation of new DNA replication initiation sites and the prevention of re-replication of DNA before mitosis. Emi1 is essential for mouse embryo development beyond the blastocyst stage [41] and for normal development in zebrafish [42].…”

Transcriptional Activation of Human CDCA8 Gene Regulated by Transcription Factor NF-Y in Embryonic Stem Cells and Cancer Cells

“…Microinjection of anti-Borealin (encoded by CDCA8) antibody into mouse zygotes arrested development at the 2-4-cell stage (16). These results indicate that CDCA8 may play a crucial role in hESCs and early embryonic development.…”

“…We previously showed that CDCA8 is highly expressed in undifferentiated human ES cells (hESCs) and early mouse embryos but is expressed at low levels in differentiated hESCs (dhESCs) (15,16). Microinjection of anti-Borealin (encoded by CDCA8) antibody into mouse zygotes arrested development at the 2-4-cell stage (16).…”

Borealin regulates bipolar spindle formation but may not act as chromosomal passenger during mouse oocyte meiosis

“…The results are also consistent with previous work in human mitosis (10) and in mouse embryo. (25) The most important roles of the CPC are the regulation of the spindle assembly checkpoint and of chromosomal alignment. (26,27) Our previous work also showed that survivin is involved in the regulation of the spindle checkpoint in mouse oocyte meiosis (19).…”