Transcription factor AP-2 is an essential and direct regulator of epidermal development in Xenopus.
Expression of the Xenopus homolog of the mammalian transcription factor AP-2alpha (XAP-2) is activated throughout the animal hemisphere shortly after the midblastula transition, and becomes restricted to prospective epidermis by the end of gastrulation, under the control of BMP signal modulation. Elevated expression in the future neural crest region begins at this time. Ectopic expression of XAP-2 can restore transcription of epidermal genes in neuralized ectoderm, both in ectodermal explants and in the intact embryo. Likewise, loss of XAP-2 function, accomplished by injection of antisense oligonucleotides or by overexpression of antimorphic XAP-2 derivatives, leads to loss of epidermal and gain of neural gene expression. These treatments also result in gastrulation failure. Thus, AP-2 is a critical regulator of ectodermal determination that is required for normal epidermal development and morphogenesis in the frog embryo.
PubMed ID: 11969261
Article link: Dev Biol.
Grant support: HL 42252 NHLBI NIH HHS
Genes referenced: bmp4 chrd dlx3 dlx5 klf6 msx1 tbx2 tfap2a xk81a1 zic1
Article Images: [+] show captions
|FIG. 1. Early expression of XAP-2. Whole mount in situ hybridizations at stage 10.25 (A) and stage 12.5–13 (B) to antisense XAP-2 probe, stained with BM-purple. In panel A, the arrowhead indicates hybridization to a chordin probe to mark the dorsal lip (magentaphos stain). At the beginning of gastrulation, XAP-2 RNA was found throughout the ectoderm, then becomes excluded from the neural plate by the end of gastrulation, at which time high level expression commences in the cranial neural crest region.|
|FIG. 6. Loss-of-function analysis; intact embryos. Fertilized eggs were injected with either (A) 600 pg of ASO281, (B) a mixture of 600 pg ASO281 and 100 pg of XAP-2* RNA, or (C) 600 pg ASO281 with 50 pg each XK81 and XK76, and cultured to stage 20. Control, uninjected embryos are shown in panel D. ASO281 treatment resulted in extensive gastrulation failure in 29/29 of the embryos, with pigmented ectoderm collapsed into a small sac. Co-injection of XAP-2* RNA rescued essentially normal development in about 12/31 of embryos, partially rescued another 9/31, and had little effect on the remainder. An example of each is shown in panel B. Keratin mRNA injection had little if effect; 24/27 were essentially identical to embryos injected with ASO281 alone, although the remaining three showed some a more moderate phenotype. One of the three partially normal embryos is shown in panel C (embryo on the right).|