Nucleic Acids Research, 2009, Vol. 37, No. 1 127 Figure 6. DNM3os, miR-199a and miR-214 are transcribed in speciﬁc tissues during embryonic development. (A) miR-199a-5p, miR-199a-3p and miR-214 levels were measured by quantitative PCR in whole embryos at embryonic stage E10.5, E11.5, E12.5, E14.5 and E16.5. (B) Shows the expression of DNM3os, miR-199a-5p, miR-199a-3p and miR-214 expression in E12.5 embryos visualized following whole-mount in situ hybridization. miR-199a and mir-214 may play a role in mediating coronal sutural formation (13). Together, these results support a role for miR-199a/214 in specifying cell fate during embryonic development. MiRBase shows that there are three genomic loci for the miR-199a gene and only one for miR-214 within the DNM-3 intron. It is therefore possible that Twist-1 expression will be found to be associated with miR-214 expression in adult tissues. Interestingly, the altered expression of miRNAs and Twist-1 in mature tissues is known to lead to changes in the expression of cell cycle proteins and tumorigenesis (23,24). Such studies have shown that miR-214 induces cell survival and cisplatin resistance via the control of PTEN expression and subsequent activation of the Akt pathway. MiR-199a targets the 30UTR of the Met proto-oncogene and its expression results in the down- regulation of Met and its down stream target ERK2 (22). Furthermore, the expression of miR-214 and miR- 199a have been shown to mirror each other in human epithelial ovarian cancer tissue (24,25), and human solid cancer tissues (26). Signiﬁcantly, Twist-1 expression has also been shown to play a role in tumour development, progression and survival (27). Together, these data suggest that miR-199a and miR-214 sculpt developmental pro- cesses by mediating eﬀects on cell cycle proteins. Furthermore, it will be important to investigate whether that the ectopic expression of miR-199a/214 during tumir- ogenesis is due to aberrant Twist-1 expression. FUNDING The Wellcome Trust. Funding for open access charge: Wellcome Trust. Conﬂict of interest statement. None declared REFERENCES 1. Bhattacharyya,S.N., Habermacher,R., Martine,U., Closs,E.I. and Filipowicz,W. (2006) Relief of microRNA-mediated translational repression in human cells subjected to stress. Cell, 125, 1111–1124. 2. Krutzfeldt,J., Poy,M.N. and Stoﬀel,M. (2006) Strategies to deter- mine the biological function of microRNAs. Nat. Genet., 38(Suppl), S14–S19.