Transplacental RNAi: deciphering gene function in the postimplantation-staged embryo.

RNAi offers the opportunity to examine the role in postimplantation development of genes that cause preimplantation lethality and to create allelic series of targeted embryos. We have delivered constituitively expressed short hairpin (sh) RNAs to pregnant mice during the early postimplantation period of development and observed gene knockdown and defects that phenocopy the null embryo. We have silenced genes that have not yet been "knocked out" in the mouse (geminin and Wnt8b), those required during earlier cleavage stages of development (nanog), and genes required at implantation (Bmp4, Bmp7) singly and in combination (Bmp4 + Bmp7), and obtained unique phenotypes.

SB-236057: Critical window of sensitivity study and embryopathy of a potent musculoskeletal teratogen.

Background: SB-236057 is a potent skeletal teratogen in rodents and rabbits. The study objective was to identify the critical developmental window of compound sensitivity and to characterize the early onset of SB-236057 embryopathy.

Methods: SB-236057 was orally administered to Sprague Dawley dams at 100 mg/kg/day on days 6-7, 8-11, 12-14, or 15-17 postcoitus (pc).

RNA inhibition of BMP-4 gene expression in postimplantation mouse embryos.

Short, hairpin RNA (shRNA) directed against bone morphogenetic protein 4 (Bmp-4) was delivered to early postimplantation staged mouse embryos via tail vein injection of pregnant dams. As early as 24 h postinjection, embryos expressed a DsRed marker and later exhibited defects of neural fold elevation and closure and of cardiac morphogenesis. Immunohistochemical analysis of sectioned embryos indicated that Bmp-4 protein was depleted and gene expression analysis indicated there was a reduction in Bmp-4 mRNA and an upregulation of the Bmp-4 antagonists, noggin and chordin, in embryos exposed to the shRNA, but not in control embryos.