Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells

Several proteins implicated in the pathogenesis of polycystic kidney disease (PKD) localize to cilia. Furthermore, cilia are malformed in mice with PKD with mutations in TgN737Rpw (encoding polaris). It is not known, however, whether ciliary dysfunction occurs or is relevant to cyst formation in PKD. Here, we show that polycystin-1 (PC1) and polycystin-2 (PC2), proteins respectively encoded by Pkd1 and Pkd2, mouse orthologs of genes mutated in human autosomal dominant PKD, co-distribute in the primary cilia of kidney epithelium. Cells isolated from transgenic mice that lack functional PC1 formed cilia but did not increase Ca(2+) influx in response to physiological fluid flow. Blocking antibodies directed against PC2 similarly abolished the flow response in wild-type cells as did inhibitors of the ryanodine receptor, whereas inhibitors of G-proteins, phospholipase C and InsP(3) receptors had no effect. These data suggest that PC1 and PC2 contribute to fluid-flow sensation by the primary cilium in renal epithelium and that they both function in the same mechanotransduction pathway. Loss or dysfunction of PC1 or PC2 may therefore lead to PKD owing to the inability of cells to sense mechanical cues that normally regulate tissue morphogenesis.     

A larval Devonian lungfish

Perhaps the most enduring of puzzles in palaeontology has been the identity of Palaeospondylus gunni Traquair, a tiny (5-60-mm) vertebrate fossil from the Middle Devonian period (approximately 385 Myr ago) of Scotland, first discovered in 1890 (refs 1-3). It is known principally from a single site (Achanarras Quarry, Caithness) where, paradoxically, it is extremely abundant, preserved in varved lacustrine deposits along with 13 other genera of fishes. Here we show that Palaeospondylus is the larval stage of a lungfish, most probably Dipterus valenciennesi Sedgwick and Murchison 1828 (ref. 5), and that development of the adult form requires a distinct metamorphosis. Palaeospondylus is the oldest known true larva of a vertebrate.     

Global anisotropy and the thickness of continents

For decades there has been a vigorous debate about the depth extent of continental roots. The analysis of heat-flow, mantle-xenolith and electrical-conductivity data all indicate that the coherent, conductive part of continental roots (the 'tectosphere') is at most 200-250 km thick. Some global seismic tomographic models agree with this estimate, but others suggest that a much thicker zone of high velocities lies beneath continental shields, reaching a depth of at least 400 km. Here we show that this disagreement can be reconciled by taking into account seismic anisotropy. We show that significant radial anisotropy, with horizontally polarized shear waves travelling faster than those that are vertically polarized, is present under most cratons in the depth range 250-400 km--similar to that found under ocean basins at shallower depths of 80-250 km. We propose that, in both cases, the anisotropy is related to shear in a low-viscosity asthenospheric channel, located at different depths under continents and oceans. The seismically defined 'tectosphere' is then at most 200-250 km thick under old continents. The 'Lehmann discontinuity', observed mostly under continents at about 200-250 km, and the 'Gutenberg discontinuity', observed under oceans at depths of about 60-80 km, may both be associated with the bottom of the lithosphere, marking a transition to flow-induced asthenospheric anisotropy.