E-GEOD-37174 - The effect of deficiency of two ATF6 homologues at early developmental stage
Released on 20 February 2013, last updated on 2 June 2014
Mammalian ATF6α/β are membrane-bound transcription factors which are activated by endoplasmic reticulum (ER) stress-induced proteolysis to upregulate various ER quality control proteins to maintain the homeostasis of the ER. ATF6α- and ATF6β-single knockout mice develop normally but ATF6α/β-double knockout causes embryonic lethality, the reason for which remains unknown. Here, we showed that medaka fish exhibits the same phenotype regarding the effects of deleting ATF6α, ATF6β, and both. Analyses revealed that ER stress occurred physiologically during early embryonic development, particularly in the brain, otic vesicle and notochord. The absence of transcriptional induction of ER chaperones in ATF6α/β-double knockout blocked notochord development, which was partially rescued by microinjection-mediated overexpression of the major ER chaperone BiP. Thus, ATF6α/β-mediated adjustment of chaperones to the increased demands in the ER is essential for development of the notochord, which synthesizes and secretes large amounts of extracellular matrix proteins to serve as the body axis. Gene expression profile at stage 24 of DKO fish (ATF6a -/-b-/-) and control fish (ATF6a+/- b+/-) was determined. Two independent experiments were performed.
transcription profiling by array
Tokiro Ishikawa <firstname.lastname@example.org>, Kazutoshi Mori