Regulation of apoptosis in theXenopusembryo by Bix3

Abstract

Members of the Bix family of homeobox-containing genes are expressed in the vegetal hemisphere of the Xenopus embryo at the early gastrula stage. Misexpression of at least some of the family members causes activation of mesoderm- and endoderm-specific genes and it is known that some of the proteins, including Bix2 and Bix3, interact with Smad proteins via a motif that is also present in the related protein Mixer. In this paper we study the function of Bix3. Misexpression of Bix3, similar to misexpression of other members of the Bixfamily, causes the activation of a range of mesendodermal genes, but the spectrum of genes induced by Bix3 differs from that induced by Bix1. More significantly, we find that overexpression of Bix3 also causes apoptosis, as does depletion of Bix3 by use of antisense morpholino oligonucleotides. The ability of Bix3 to causes apoptosis is not associated with its ability to activate transcription and nor with its possession of a Smad interaction motif. Rather, Bix3 lacks a C-terminal motif,which, in Bix1, acts in cis to inhibit apoptosis. Mutation of this sequence in Bix1 causes the protein to acquire apoptosis-inducing activity.

KHDC1B Is a Novel CPEB Binding Partner Specifically Expressed in Mouse Oocytes and Early Embryos

“…By stage 8.5, these effected cells had died and the embryos failed to gastrulate (Figure 5A and data not shown). This phenotype resembles the induction of apoptosis achieved by overexpressing Bix3 (Trindade et al , 2003) and would be consistent with the fact that overexpression of KHDC1A has been shown to induce apoptosis in tissue culture cells (Rajpal et al , 2003). In contrast to KHDC1A, ectopic expression of KHDC1B resulted in large blastomeres at the injection site (Figure 5A).…”

Defining Synphenotype Groups in Xenopus tropicalis by Use of Antisense Morpholino Oligonucleotides

“…This may occur, for example, if the targeted gene is expressed in a restricted manner and the presence of the gene product elsewhere in the embryo causes an over-expression phenotype [27]. Successful rescue may also depend on the concentration of rescuing RNA [28]. We have only adopted this approach to investigate the specificities of the MOs that lead to defects in gastrulation (see below).…”

Apoptosis in amphibian development

“…Several experiments based upon the over-expression of FoxO genes in X. laevis showed these genes were indispensable for tissue differentiation but not for gastrulation, even overexpression of several of them induced severe damages in gastrulae [25]. Bix expressed in early Xenopus gastrula, and an over-expression as well as a depletion of Bix3 causes apoptosis [26].…”