Subfunctionalization of duplicated genes as a transition state to neofunctionalization

Background  

Gene duplication has been suggested to be an important process in the generation of evolutionary novelty. Neofunctionalization, as an adaptive process where one copy mutates into a function that was not present in the pre-duplication gene, is one mechanism that can lead to the retention of both copies. More recently, subfunctionalization, as a neutral process where the two copies partition the ancestral function, has been proposed as an alternative mechanism driving duplicate gene retention in organisms with small effective population sizes. The relative importance of these two processes is unclear.     

Dominant-negative isoforms of Tcf/Lef proteins in development and disease

Comment on: Vacik T, et al. Genes Dev 2011; 25:1783-95.     

Expression of Tcf/Lef and sFrp and localization of beta-catenin in the developing mouse lung.

Recent evidence that Wnts and other genes in the Wnt signaling pathway are expressed in embryonic and adult mouse lung suggests that this pathway is important for cell fate decisions and differentiation of lung cell types. We therefore examined the expression and protein distribution of several Wnt pathway components during prenatal mouse lung development using whole-mount in situ hybridization and immunohistochemistry. Between embryonic days 10.5 and 17.5 (E10.5-E17.5), beta-catenin was localized in the cytoplasm, and often also the nucleus, of the undifferentiated primordial epithelium (PE), differentiating alveolar epithelium (AE; present from E14.5 onward), and adjacent mesenchyme. Tcf1, Lef1, Tcf3, Tcf4, sFrp1, sFrp2 and sFrp4 were also expressed in the PE, AE, and adjacent mesenchyme in specific spatio-temporal patterns.     

Involvement of Tcf/Lef in establishing cell types along the animal-vegetal axis of sea urchins

Members of the Tcf/Lef family interact with β-catenin to activate programs of gene expression during development. Recently β-catenin was shown to be essential for establishing cell fate along the animal-vegetal axis of the sea urchin embryo. To examine the role of Tcf/Lef in sea urchins we cloned a Strongylocentrotus purpuratus Tcf/Lef homolog. Expression of SpTcf/Lef was maximal when β-catenin became localized to nuclei of vegetal blastomeres, consistent with its acting in combination with β-catenin to specify vegetal cell fates. Expression of a dominant-negative SpTcf/Lef inhibited primary and secondary mesenchyma, endoderm, and aboral ectoderm formation in a manner similar to that observed when nuclear accumulation of β-catenin was prevented. Our results suggest that SpTcf/Lef functions by interacting with β-catenin to specify cell fates along the sea urchin animal-vegetal axis. Received: 6 July 1999 / Accepted: 27 August 1999