The Atr-Chek1 pathway inhibits axon regeneration in response to Piezo-dependent mechanosensation.

Atr is a serine/threonine kinase, known to sense single-stranded DNA breaks and activate the DNA damage checkpoint by phosphorylating Chek1, which inhibits Cdc25, causing cell cycle arrest. This pathway has not been implicated in neuroregeneration. We show that in Drosophila sensory neurons removing Atr or Chek1, or overexpressing Cdc25 promotes regeneration, whereas Atr or Chek1 overexpression, or Cdc25 knockdown impedes regeneration. Inhibiting the Atr-associated checkpoint complex in neurons promotes regeneration and improves synapse/behavioral recovery after CNS injury. Independent of DNA damage, Atr responds to the mechanical stimulus elicited during regeneration, via the mechanosensitive ion channel Piezo and its downstream NO signaling. Sensory neuron-specific knockout of Atr in adult mice, or pharmacological inhibition of Atr-Chek1 in mammalian neurons in vitro and in flies in vivo enhances regeneration. Our findings reveal the Piezo-Atr-Chek1-Cdc25 axis as an evolutionarily conserved inhibitory mechanism for regeneration, and identify potential therapeutic targets for treating nervous system trauma.

Lgr6 marks epidermal stem cells with a nerve-dependent role in wound re-epithelialization.

Stem cells support lifelong maintenance of adult organs, but their specific roles during injury are poorly understood. Here we demonstrate that Lgr6 marks a regionally restricted population of epidermal stem cells that interact with nerves and specialize in wound re-epithelialization. Diphtheria toxin-mediated ablation of Lgr6 stem cells delays wound healing, and skin denervation phenocopies this effect. Using intravital imaging to capture stem cell dynamics after injury, we show that wound re-epithelialization by Lgr6 stem cells is diminished following loss of nerves. This induces recruitment of other stem cell populations, including hair follicle stem cells, which partially compensate to mediate wound closure. Single-cell lineage tracing and gene expression analysis reveal that the fate of Lgr6 stem cells is shifted toward differentiation following loss of their niche. We conclude that Lgr6 epidermal stem cells are primed for injury response and interact with nerves to regulate their fate.

Two-photon live imaging of single corneal stem cells reveals compartmentalized organization of the limbal niche.

The functional heterogeneity of resident stem cells that support adult organs is incompletely understood. Here, we directly visualize the corneal limbus in the eyes of live mice and identify discrete stem cell niche compartments. By recording the life cycle of individual stem cells and their progeny, we directly analyze their fates and show that their location within the tissue can predict their differentiation status. Stem cells in the inner limbus undergo mostly symmetric divisions and are required to sustain the population of transient progenitors that support corneal homeostasis. Using in situ photolabeling, we captured their progeny exiting the niche before moving centripetally in unison. The long-implicated slow-cycling stem cells are functionally distinct and display local clonal dynamics during homeostasis but can contribute to corneal regeneration after injury. This study demonstrates how the compartmentalized organization of functionally diverse stem cell populations supports the maintenance and regeneration of an adult organ.

Caenorhabditis elegans glutamylating enzymes function redundantly in male mating.

Microtubule glutamylation is an important modulator of microtubule function and has been implicated in the regulation of centriole stability, neuronal outgrowth and cilia motility. Glutamylation of the microtubules is catalyzed by a family of tubulin tyrosine ligase-like (TTLL) enzymes. Analysis of individual TTLL enzymes has led to an understanding of their specific functions, but how activities of the TTLL enzymes are coordinated to spatially and temporally regulate glutamylation remains relatively unexplored. We have undertaken an analysis of the glutamylating TTLL enzymes in C. elegans We find that although all five TTLL enzymes are expressed in the embryo and adult worm, loss of individual enzymes does not perturb microtubule function in embryonic cell divisions. Moreover, normal dye-filling, osmotic avoidance and male mating behavior indicate the presence of functional amphid cilia and male-specific neurons. A ttll-4(tm3310); ttll-11(tm4059); ttll-5(tm3360) triple mutant, however, shows reduced male mating efficiency due to a defect in the response step, suggesting that these three enzymes function redundantly, and that glutamylation is required for proper function of the male-specific neurons.

Heteroepitaxial growth of GaP/ZnS nanocable with superior optoelectronic response.

We demonstrate the controlled growth of coaxial nanocables composed of GaP/ZnS core-shell structures by a facile chemical vapor deposition method. Structural analysis confirms that the cubic GaP (111) plane and wurtzite ZnS (0001) plane present close similarities in terms of hexagonal-arranged atomic configuration with small in-plane lattice mismatch, and the ZnS shell is epitaxially grown on the (100) plane of the cubic GaP core. Compared with the unitary ZnS nanobelts, the GaP/ZnS coaxial nanocables exhibit improved optoelectronic properties such as high photocurrent and excellent photocurrent stability. This approach opens up new strategy to boost the performance of ZnS-based photodetectors.

Controlled synthesis of AlN/GaN multiple quantum well nanowire structures and their optical properties.

We report the controlled synthesis of AlN/GaN multi-quantum well (MQW) radial nanowire heterostructures by metal-organic chemical vapor deposition. The structure consists of a single-crystal GaN nanowire core and an epitaxially grown (AlN/GaN)(m) (m = 3, 13) MQW shell. Optical excitation of individual MQW nanowires yielded strong, blue-shifted photoluminescence in the range 340-360 nm, with respect to the GaN near band-edge emission at 368.8 nm. Cathodoluminescence analysis on the cross-sectional MQW nanowire samples showed that the blue-shifted ultraviolet luminescence originated from the GaN quantum wells, while the defect-associated yellow luminescence was emitted from the GaN core. Computational simulation provided a quantitative analysis of the mini-band energies in the AlN/GaN superlattices and suggested the observed blue-shifted emission corresponds to the interband transitions between the second subbands of GaN, as a result of quantum confinement and strain effect in these AlN/GaN MQW nanowire structures.

The interplay of structural and optical properties in individual ZnO nanostructures.

Semiconductor nanostructures exhibit unique properties distinct from their bulk counterparts by virtue of nanoscale dimensions; in particular, exceptionally large surface area-to-volume ratios relative to that of the bulk produce variations in surface state populations that have numerous consequences on materials properties. Of the low-dimensional semiconductor nanostructures, nanowires offer a unique prospect in nanoscale optoelectronics due to their one-dimensional architecture. Already, many devices based upon individual nanowires have been demonstrated, but questions about how nano-size and structural variations affect the underlying materials properties still remain unanswered. Here, we focus on understanding the growth mechanism and kinetics of ZnO nanowires and related nanowalls, and their effects on nanoscale structural and optical properties.

Direct correlation between structural and optical properties of III-V nitride nanowire heterostructures with nanoscale resolution.

Direct correlation of structural and optical properties on the nanoscale is essential for rational synthesis of nanomaterials with predefined structure and functionality. We study optical properties of single III-V nitride nanowire radial heterostructures with measured spatial resolution of <20 nm using cathodoluminescence (CL) technique coupled with scanning transmission electron microscopy (STEM). Enhanced carrier recombination in nanowire quantum wells and reduced light emission from regions containing structural defects were directly observed. Using newly developed parallel-detection-mode CL-STEM, we show that optical properties can vary within a single nanowire heterostructure as a function of nanowire morphology.

Controlled growth of ternary alloy nanowires using metalorganic chemical vapor deposition.

We report the growth and characterization of ternary AlxGa1- xAs nanowires by metalorganic chemical vapor deposition as a function of temperature and V/III ratio. Transmission electron microscopy and energy dispersive X-ray spectroscopy show that, at high temperatures and high V/III ratios, the nanowires form a core-shell structure with higher Al composition in the nanowire core than in the shell. We develop a growth model that takes into account diffusion of reactants and decomposition rates at the nanowire catalyst and stem to describe the compositional difference and the shell growth rate. Utilizing this model, we have successfully grown compositionally uniform Al0.16Ga0.84As nanowires. The ability to rationally tune the composition of ternary alloy nanowires broadens the application range of nanowires by enabling more complex nanowire heterostructures.

Surface-emitting fiber lasers.

All fiber lasers to date emit radiation only along the fiber axis. Here a fiber that exhibits laser emission that is radially directed from its circumferential surface is demonstrated. A unique and controlled azimuthally anisotropic optical wave front results from the interplay between a cylindrical photonic bandgap fiber resonator, anisotropic organic dye gain, and a linearly polarized axial pump. Low threshold (86nJ) lasing at nine different wavelengths is demonstrated throughout the visible and near-infrared spectra. We also report the experimental realization of unprecedented layer thicknesses of 29.5 nm maintained throughout meter-long fibers. Such a device may have interesting medical applications ranging from photodynamic therapy to in vivo molecular imaging, as well as textile fabric displays.