The existence of life in extreme conditions, in particular in extraterrestrial environments, is certainly one of the most intriguing scientific questions of our time. In this report, we demonstrate the use of an innovative nanoscale motion sensor in life-searching experiments in Earth-bound and interplanetary missions. This technique exploits the sensitivity of nanomechanical oscillators to transduce the small fluctuations that characterize living systems. The intensity of such movements is an indication of the viability of living specimens and conveys information related to their metabolic activity. Here, we show that the nanomotion detector can assess the viability of a vast range of biological specimens and that it could be the perfect complement to conventional chemical life-detection assays. Indeed, by combining chemical and dynamical measurements, we could achieve an unprecedented depth in the characterization of life in extreme and extraterrestrial environments.nanomechanical sensors | extraterrestrial life | nanoscale fluctuations | living specimens | nanomotion detector T he existence of life in extreme conditions, in particular in extraterrestrial environments, is certainly one of the most intriguing scientific questions of our time. Indeed, the work of many scientists and organizations is focused on the discovery and on the consequent study of extremophiles and extraterrestrial organisms. The direct research for these kinds of life forms is usually conducted by deploying robotic crafts. These man-made vessels contain a suite of scientific analytical instrumentation that is specifically conceived to trace life signatures contained in the geological record. For instance, the search for life in our solar system started in 1975 with the Viking program and continues today. Future missions are planned to explore the presence of life on satellites of the giant planets, such as Europa (Jupiter) or Titan and Enceladus (Saturn). The biological instrumentation that is included in these vessels is complex, but up to now, it is mainly devoted to the chemical detection of molecules involved in living metabolism, as we know it on Earth.In this report, we show how a technique, the nanomotion detector, can be used in new life-searching instrumentation in Earth-bound and interplanetary missions. The technique exploits the sensitivity of nanomechanical sensors to transduce the small movements that characterize living systems. The intensity of such movements is an indication of the viability of the specimens and conveys information related to their metabolic activity. Here, we demonstrate that this simple technique can assess the viability of a vast range of biological specimens and that it could be the perfect complement to conventional chemical assays. Moreover, due to the simplicity of its working principle, a device based on this technology has negligible weight and requires very low electrical power, compared with other life-detector systems.Nanomechanical oscillators are extremely sensitive devices that are commonl...

Ciliated ependymal cells play central functions in the control of cerebrospinal fluid homeostasis in the mammalian brain, and defects in their differentiation or ciliated properties can lead to hydrocephalus. Regulatory factor X (RFX) transcription factors regulate genes required for ciliogenesis in the nematode, drosophila and mammals. We show here that Rfx3-deficient mice suffer from hydrocephalus without stenosis of the aqueduct of Sylvius. RFX3 is expressed strongly in the ciliated ependymal cells of the subcommissural organ (SCO), choroid plexuses (CP) and ventricular walls during embryonic and postnatal development. Ultrastructural analysis revealed that the hydrocephalus is associated with a general defect in CP differentiation and with severe agenesis of the SCO. The specialized ependymal cells of the CP show an altered epithelial organization, and the SCO cells lose their characteristic ultrastructural features and adopt aspects more typical of classical ependymal cells. These differentiation defects are associated with changes in the number of cilia, although no obvious ultrastructural defects of these cilia can be observed in adult mice. Moreover, agenesis of the SCO is associated with downregulation of SCO-spondin expression as early as E14.5 of embryonic development. These results demonstrate that RFX3 is necessary for ciliated ependymal cell differentiation in the mouse.

The transcription factor regulatory factor X (RFX)-3 regulates the expression of genes required for the growth and function of cilia. We show here that mouse RFX3 is expressed in developing and mature pancreatic endocrine cells during embryogenesis and in adults. RFX3 expression already is evident in early Ngn3-positive progenitors and is maintained in all major pancreatic endocrine cell lineages throughout their development. Primary cilia of hitherto unknown function present on these cells consequently are reduced in number and severely stunted in Rfx3 Ϫ/Ϫ mice. This ciliary abnormality is associated with a developmental defect leading to a uniquely altered cellular composition of the islets of Langerhans. Just before birth, Rfx3 Ϫ/Ϫ islets contain considerably less insulin-, glucagon-, and ghrelinproducing cells, whereas pancreatic polypeptide-positive cells are markedly increased in number. In adult mice, the defect leads to small and disorganized islets, reduced insulin production, and impaired glucose tolerance. These findings suggest that RFX3 participates in the mechanisms that govern pancreatic endocrine cell differentiation and that the presence of primary cilia on islet cells may play a key role in this process. Diabetes 56:950 -959, 2007

The corpus callosum (CC) is the major commissure that bridges the cerebral hemispheres. Agenesis of the CC is associated with human ciliopathies, but the origin of this default is unclear. Regulatory Factor X3 (RFX3) is a transcription factor involved in the control of ciliogenesis, and Rfx3–deficient mice show several hallmarks of ciliopathies including left–right asymmetry defects and hydrocephalus. Here we show that Rfx3–deficient mice suffer from CC agenesis associated with a marked disorganisation of guidepost neurons required for axon pathfinding across the midline. Using transplantation assays, we demonstrate that abnormalities of the mutant midline region are primarily responsible for the CC malformation. Conditional genetic inactivation shows that RFX3 is not required in guidepost cells for proper CC formation, but is required before E12.5 for proper patterning of the cortical septal boundary and hence accurate distribution of guidepost neurons at later stages. We observe focused but consistent ectopic expression of Fibroblast growth factor 8 (Fgf8) at the rostro commissural plate associated with a reduced ratio of GLIoma-associated oncogene family zinc finger 3 (GLI3) repressor to activator forms. We demonstrate on brain explant cultures that ectopic FGF8 reproduces the guidepost neuronal defects observed in Rfx3 mutants. This study unravels a crucial role of RFX3 during early brain development by indirectly regulating GLI3 activity, which leads to FGF8 upregulation and ultimately to disturbed distribution of guidepost neurons required for CC morphogenesis. Hence, the RFX3 mutant mouse model brings novel understandings of the mechanisms that underlie CC agenesis in ciliopathies.