Abstract
In vivo function of CDK5 and Abl enzyme substrate 2 (Cables2), belonging to the Cables protein family, is unknown. Here, we found that targeted disruption of the entire Cables2 locus (Cables2d) caused growth retardation and enhanced apoptosis at the gastrulation stage and then induced embryonic lethality in mice. Comparative transcriptome analysis revealed disruption of Cables2, 50% down-regulation of Rps21 abutting on the Cables2 locus, and up-regulation of p53-target genes in Cables2d gastrulas. We further revealed the lethality phenotype in Rps21-deleted mice and unexpectedly, the exon 1-deleted Cables2 mice survived. Interestingly, chimeric mice derived from Cables2d ESCs carrying exogenous Cables2 and tetraploid wild-type embryo overcame gastrulation. These results suggest that the diminished expression of Rps21 and the completed lack of Cables2 expression are intricately involved in the embryonic lethality via the p53 pathway. This study sheds light on the importance of Cables2 locus in mouse embryonic development.
Highlights
The mouse embryo at the blastocyst stage, consists of two layers: the outer trophectoderm and the inner cell mass (ICM)
We first investigated the expression of CDK5 and Abl enzyme substrate 2 (Cables2) in mouse embryonic stem cells (ESCs), blastocysts, and embryos at E7.5 by reverse transcription polymerase chain reaction (RT-PCR)
The results indicated that Cables2 was expressed in all three stages of early development (Figure 1A)
Summary
The mouse embryo at the blastocyst stage, consists of two layers: the outer trophectoderm and the inner cell mass (ICM). The ICM is characterized as pluripotent stem cells, from which the epiblast and primitive endoderm are derived (Chazaud et al, 2006; Evans and Kaufman, 1981; Rossant et al, 2003). Wnt, Nodal, and bone morphogenetic protein (BMP) signaling pathways are essential and coordinately control formation of the proximal–distal (P–D) axis during the egg cylinder stage and the subsequent conversion of this axis into the anterior–posterior (A–P) axis early in gastrulation (reviewed in Arkell and Tam, 2012; Robertson, 2014; Shen, 2007; Ten Berge et al, 2008; Wang et al, 2012; Winnier et al, 1995). Nodal and Wnt activity levels are dependent upon the BMP pathway interactions (Robertson, 2014; Tam and Loebel, 2007). While some murine axis and gastrulation signaling events are known, many other processes remain undiscovered
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