Kwang-Wook Choi

Novel Cytochrome P450, cyp6a17, Is Required for Temperature Preference Behavior in Drosophila

Perception of temperature is an important brain function for organisms to survive. Evidence suggests that temperature preference behavior (TPB) in Drosophila melanogaster, one of poikilothermal animals, is regulated by cAMP-dependent protein kinase (PKA) signaling in mushroom bodies of the brain. However, downstream targets for the PKA signaling in this behavior have not been identified. From a genome-wide search for the genes regulated by PKA activity in the mushroom bodies, we identified the cyp6a17 Cytochrome P450 gene as a new target for PKA. Our detailed analysis of mutants by genetic, molecular and behavioral assays shows that cyp6a17 is essential for temperature preference behavior. cyp6a17 expression is enriched in the mushroom bodies of the adult brain. Tissue-specific knockdown and rescue experiments demonstrate that cyp6a17 is required in the mushroom bodies for normal temperature preference behavior. This is the first study, to our knowledge, to show PKA-dependent expression of a cytochrome P450 gene in the mushroom bodies and its role as a key factor for temperature preference behavior. Taken together, this study reveals a new PKA-Cytochrome P450 pathway that regulates the temperature preference behavior.

Drosophila Schip1 Links Expanded and Tao-1 to Regulate Hippo Signaling.

Regulation of organ size is essential in animal development, and Hippo (Hpo) signaling is a major conserved mechanism for controlling organ growth. In Drosophila, Hpo and Warts kinases are core components of this pathway and function as tumor suppressors by inhibiting Yorkie (Yki). Expanded (Ex) is a regulator of the Hpo activity, but how they are linked is unknown. Here, we show that Schip1, a Drosophila homolog of the mammalian Schwannomin interacting protein 1 (SCHIP1), provides a link between Ex and Hpo. Ex is required for apical localization of Schip1 in imaginal discs. Schip1 is necessary for promoting membrane localization and phosphorylation of Hpo by recruiting the Hpo kinase Tao-1. Taking these findings together, we conclude that Schip1 directly links Ex to Hpo signaling by recruiting Tao-1. This study provides insights into the mechanism of Tao-1 regulation and a potential growth control function for SCHIP1 in mammals.

Versatile Transfer of an Ultralong and Seamless Nanowire Array Crystallized at High Temperature for Use in High-Performance Flexible Devices

Nanowire (NW) transfer technology has provided promising strategies to realize future flexible materials and electronics. Using this technology, geometrically controlled, high-quality NW arrays can now be obtained easily on various flexible substrates with high throughput. However, it is still challenging to extend this technology to a wide range of high-performance device applications because its limited temperature tolerance precludes the use of high-temperature annealing, which is essential for NW crystallization and functionalization. A pulsed laser technique has been developed to anneal NWs in the presence of a flexible substrate; however, the induced temperature is not high enough to improve the properties of materials such as ceramics and semiconductors. Here, we present a versatile nanotransfer method that is applicable to NWs that require high-temperature annealing. To successfully anneal NWs during their transfer, the developed fabrication method involves sequential removal of a nanoscale sacrificial layer. Using this method, we first produce an ultralong, perfectly aligned polycrystalline barium titanate (BaTiO3) NW array that is heat treated at 700 °C on a flexible polyethylene terephthalate (PET) substrate. This high-quality piezoelectric NW array on a flexible substrate is used as a flexible nanogenerator that generates current and voltage 37 and 10 times higher, respectively, than those of a nanogenerator made of noncrystallized BaTiO3 NWs.

High-Performance Hybrid Complementary Logic Inverter through Monolithic Integration of a MEMS Switch and an Oxide TFT

A hybrid complementary logic inverter consisting of a microelectromechanical system switch as a promising alternative for the p-type oxide thin film transistor (TFT) and an n-type oxide TFT is presented for ultralow power integrated circuits. These heterogeneous microdevices are monolithically integrated. The resulting logic device shows a distinctive voltage transfer characteristic curve, very low static leakage, zero-short circuit current, and exceedingly high voltage gain.

Cell Type-Specific Responses to Wingless, Hedgehog and Decapentaplegic Are Essential for Patterning Early Eye-Antenna Disc in Drosophila

The Drosophila eye-antenna imaginal disc (ead) is a flattened sac of two-layered epithelia, from which most head structures are derived. Secreted morphogens like Wingless (Wg), Hedgehog (Hh), and Decapentaplegic (Dpp) are important for early patterning of ead, but the underlying mechanisms are still largely unknown. To understand how these morphogens function in the ead of early larval stages, we used wg-LacZ and dpp-Gal4 markers for the examination of wild-type and mutant eads. We found that the ead immediately after hatching was crescent-shaped with the Bolwig’s nerve at the ventral edge, suggesting that it consists of dorsal domain. In a subsequent step, transcriptional induction of dpp in the cells along the Bolwig’s nerve was followed by rapid growth of the ventral domain. Both Wg and Hh were required for the formation of the ventral domain. Wg was crucial for the growth of the entire ead, but Hh was essential for cell division only in the dorsal domain. In the ventral domain, Hh regulated dpp transcription. Based on these data, we propose that signaling among distinct groups of cells expressing Wg, Dpp, or Hh in the ead of the first-instar larvae are critical for coordinated growth and patterning of ead.

A simple breathing rate-sensing method exploiting a temporarily condensed water layer formed on an oxidized surface

We describe a very simple breathing rate-sensing method that detects a significant electric current change between two metal electrodes on an oxidized surface. The current change is caused by the formation of a water layer from exhaled breath. We discovered that breathing onto the oxidized surface causes instant water condensation, and it generates 20 times increased current than that measured in the inhalation period. The condensed water quickly evaporates, enabling us to detect dynamic human breathing in real time. We also investigated the breathing rate sensor by varying the relative humidity, temperature, and breathing frequency and confirmed its potential for practical applications.

Kinesin-II recruits Armadillo and Dishevelled for wingless signaling in Drosophila

Wingless (Wg)/Wnt signaling is fundamental in metazoan development. Armadillo (Arm)/β-catenin and Dishevelled (Dsh) are key components of Wnt signal transduction. Recent studies suggest that intracellular trafficking of Wnt signaling components is important, but underlying mechanisms are not well known. Here, we show that Klp64D, the Drosophila homolog of Kif3A kinesin II subunit, is required for Wg signaling by regulating Arm during wing development. Mutations in klp64D or RNAi cause wing notching and loss of Wg target gene expression. The wing notching phenotype by Klp64D knockdown is suppressed by activated Arm but not by Dsh, suggesting that Klp64D is required for Arm function. Furthermore, klp64D and arm mutants show synergistic genetic interaction. Consistent with this genetic interaction, Klp64D directly binds to the Arm repeat domain of Arm and can recruit Dsh in the presence of Arm. Overexpression of Klp64D mutated in the motor domain causes dominant wing notching, indicating the importance of the motor activity. Klp64D shows subcellular localization to intracellular vesicles overlapping with Arm and Dsh. In klp64D mutants, Arm is abnormally accumulated in vesicular structures including Golgi, suggesting that intracellular trafficking of Arm is affected. Human KIF3A can also bind β-catenin and rescue klp64D RNAi phenotypes. Taken together, we propose that Klp64D is essential for Wg signaling by trafficking of Arm via the formation of a conserved complex with Arm.

Opposing interactions between homothorax and Lobe define the ventral eye margin of Drosophila eye

Patterning in multi-cellular organisms involves progressive restriction of cell fates by generation of boundaries to divide an organ primordium into smaller fields. We have employed the Drosophila eye model to understand the genetic circuitry responsible for defining the boundary between the eye and the head cuticle on the ventral margin. The default state of the early eye is ventral and depends on the function of Lobe (L) and the Notch ligand Serrate (Ser). We identified homothorax (hth) as a strong enhancer of the L mutant phenotype of loss of ventral eye. Hth is a MEIS class gene with a highly conserved Meis-Hth (MH) domain and a homeodomain (HD). Hth is known to bind Extradenticle (Exd) via its MH domain for its nuclear translocation. Loss-of-function of hth, a negative regulator of eye, results in ectopic ventral eye enlargements. This phenotype is complementary to the L mutant phenotype of loss-of-ventral eye. However, if L and hth interact during ventral eye development remains unknown. Here we show that (i) L acts antagonistically to hth, (ii) Hth is upregulated in the L mutant background, and (iii) MH domain of Hth is required for its genetic interaction with L, while its homeodomain is not, (iv) in L mutant background ventral eye suppression function of Hth involves novel MH domain-dependent factor(s), and (v) nuclear localization of Exd is not sufficient to mediate the Hth function in the L mutant background. Further, Exd is not a critical rate-limiting factor for the Hth function. Thus, optimum levels of L and Hth are required to define the boundary between the developing eye and head cuticle on the ventral margin.

Ebi modulates wing growth by ubiquitin-dependent downregulation of Crumbs in Drosophila

Notch signaling at the dorsoventral (DV) boundary is essential for patterning and growth of wings in Drosophila. The WD40 domain protein Ebi has been implicated in the regulation of Notch signaling at the DV boundary. Here we show that Ebi regulates wing growth by antagonizing the function of the transmembrane protein Crumbs (Crb). Ebi physically binds to the extracellular domain of Crb (Crbext), and this interaction is specifically mediated by WD40 repeats 7-8 of Ebi and a laminin G domain of Crbext. Wing notching resulting from reduced levels of Ebi is suppressed by decreasing the Crb function. Consistent with this antagonistic genetic relationship, Ebi knockdown in the DV boundary elevates the Crb protein level. Furthermore, we show that Ebi is required for downregulation of Crb by ubiquitylation. Taken together, we propose that the interplay of Crb expression in the DV boundary and ubiquitin-dependent Crb downregulation by Ebi provides a mechanism for the maintenance of Notch signaling during wing development. Summary: In the fly wing, the transmembrane protein Crumbs antagonises Notch signalling. Crumbs, in turn, is inhibited by the WD40 domain protein Ebi, thus promoting Notch activity.

Nanomechanical Encoding Method Using Enhanced Thermal Concentration on a Metallic Nanobridge

We present a fast, energy-efficient nano-thermomechanical encoding scheme for digital information storage and retrieval. Digital encoding processes are conducted by the bistable electrothermal actuation of a scalable nanobridge device. The electrothermal energy is highly concentrated by enhanced electron/phonon scattering and heat insulation in a sub-100 nm metallic layer. The efficient conversion of electrothermal energy into mechanical strain allows digital switching and programming processes within 60 ns at 0.75 V with a programming energy of only 54 pJ. Furthermore, this encoding scheme together with the thermally robust design enables data retention at temperatures up to 400 °C. These results suggest that the proposed nano-thermomechanical encoding method could contribute to low-power electronics and robust information storage/retrieval systems.