Planarian flatworms maintain their body plan in the face of constant internal turnover and can regenerate from arbitrary tissue fragments. Both phenomena require self-maintaining and self-organizing patterning mechanisms, the molecular mechanisms of which remain poorly understood. We show that a morphogenic gradient of canonical Wnt signaling patterns gene expression along the planarian anteroposterior (A/P) axis. Our results demonstrate that gradient formation likely occurs autonomously in the tail and that an autoregulatory module of Wnt-mediated Wnt expression both shapes the gradient at steady state and governs its re-establishment during regeneration. Functional antagonism between the tail Wnt gradient and an unknown head patterning system further determines the spatial proportions of the planarian A/P axis and mediates mutually exclusive molecular fate choices during regeneration. Overall, our results suggest that the planarian A/P axis is patterned by self-organizing patterning systems deployed from either end that are functionally coupled by mutual antagonism.

Biological patterns generated during development and regeneration often scale with organism size. Some organisms, e.g., flatworms, can regenerate a rescaled body plan from tissue fragments of varying sizes. Inspired by these examples, we introduce a generalization of Turing patterns that is self-organized and self-scaling. A feedback loop involving diffusing expander molecules regulates the reaction rates of a Turing system, thereby adjusting pattern length scales proportional to system size. Our model captures essential features of body plan regeneration in flatworms as observed in experiments.

The Hedgehog (Hh) pathway plays dual roles in proliferation and patterning during embryonic development, but the mechanism(s) that distinguish the mitogenic and patterning activities of Hh signalling are not fully understood. An additional level of complexity is provided by the observation that Hh signalling can both promote and inhibit cell proliferation. One model to account for this apparent paradox is that Hh signalling primarily regulates cell cycle kinetics, such that activation of Hh signalling promotes fast cycling and an earlier cell cycle exit. Here we report that activation of Hh signalling promotes endodermal cell proliferation but inhibits proliferation in neighbouring non-endodermal cells, suggesting that the cell cycle kinetics model is insufficient to account for the opposing proliferative responses to Hh signalling. We show that expression of the chemokine receptor Cxcr4a is a critical parameter that determines the proliferative response to Hh signalling, and that loss of Cxcr4a function attenuates the transcription of cell cycle regulator targets of Hh signalling without affecting general transcriptional targets. We show that Cxcr4a inhibits PKA activity independently of Hh signalling, and propose that Cxcr4a enhances Hh-dependent proliferation by promoting the activity of Gli1. Our results indicate that Cxcr4a is required for Hh-dependent cell proliferation but not for Hh-dependent patterning, and suggest that the parallel activation of Cxcr4a is required to modulate the Hh pathway to distinguish between patterning and proliferation.

Respiratory tract infections have the highest rates of antibiotic prescriptions where symptoms like fever, cough, and rigors are regularly misinterpreted and where bacterial infections cannot be distinguished from viral ones. Nevertheless, it has been recently suggested that C-reactive protein (CRP), a protein produced by the liver in response to infection, could serve as a potential biomarker for the precise differentiation of these two types of infections. Thus, its quick and accurate detection would potentially reduce the unnecessary antibiotic use. To this end, we present an easy and sensitive approach for the selective detection of C-reactive protein (CRP) by liquid-gated carbon nanotube field effect transistors (LG-CNTFET). Herein, CNT-networks were deposited between electrodes via controlled dielectrophoretic deposition and then functionalized with a novel specific antibody and a polyethylene glycol (PEG) layer in order to overcome the Debye screening. The successful fabrication and functionalization were confirmed by scanning electron microscopy. The results showed a selective and reproducible detection down to picomolar concentrations in PBS buffer without complicated microfluidics. The simplicity and high sensitivity of this sensor platform make it a promising tool for the quick and precise differential diagnosis of viral and bacterial infections.