Transcriptional regulators in the Hippo signaling pathway control organ growth in Xenopus tadpole tail regeneration.

The size and shape of tissues are tightly controlled by synchronized processes among cells and tissues to produce an integrated organ. The Hippo signaling pathway controls both cell proliferation and apoptosis by dual signal-transduction states regulated through a repressive kinase cascade. Yap1 and Tead, transcriptional regulators that act downstream of the Hippo signaling kinase cascade, have essential roles in regulating cell proliferation.

Wound healing in mammals and amphibians: toward limb regeneration in mammals.

Mammalian fetal skin regenerates perfectly, but adult skin repairs by the formation of scar tissue. The cause of this imperfect repair by adult skin is not understood. In contrast, wounded adult amphibian (urodeles and anurans) skin is like mammalian fetal skin in that it repairs by regeneration, not scarring.

Cilia at the node of mouse embryos sense fluid flow for left-right determination via Pkd2.

Unidirectional fluid flow plays an essential role in the breaking of left-right (L-R) symmetry in mouse embryos, but it has remained unclear how the flow is sensed by the embryo. We report that the Ca(2+) channel Polycystin-2 (Pkd2) is required specifically in the perinodal crown cells for sensing the nodal flow. Examination of mutant forms of Pkd2 shows that the ciliary localization of Pkd2 is essential for correct L-R patterning.

Two rotating cilia in the node cavity are sufficient to break left-right symmetry in the mouse embryo.

Determination of left-right asymmetry in mouse embryos is achieved by a leftward fluid flow (nodal flow) in the node cavity that is generated by clockwise rotational movement of 200-300 cilia in the node. The precise action of nodal flow and how much flow input is required for the robust read-out of left-right determination remains unknown. Here we show that a local leftward flow generated by as few as two rotating cilia is sufficient to break left-right symmetry.

Left-right asymmetry in the level of active Nodal protein produced in the node is translated into left-right asymmetry in the lateral plate of mouse embryos.

Left-right (L-R) asymmetry in the mouse embryo is generated in the node and is dependent on cilia-driven fluid flow, but how the initial asymmetry is transmitted from the node to the lateral plate has remained unknown. We have now identified a transcriptional enhancer (ANE) in the human LEFTY1 gene that exhibits marked L>R asymmetric activity in perinodal cells of the mouse embryo. Dissection of ANE revealed that it is activated in the perinodal cells on the left side by Nodal signaling, suggesting that Nodal activity in the node is asymmetric at a time when Nodal expression is symmetric.

SKIP modifies gene expression by affecting both transcription and splicing.

SKIP has been described as a transcriptional coregulator as well as a spliceosome component, but the relationship between these functions is not clear. We found that SKIP activated reporter gene expression from the basal promoters of viral origin. SKIP exhibited more prominent effect on the promoters with stronger activities, in an experiment employing a series of reporter constructs carrying different numbers of GC boxes.