Uniform estimates of nonlinear spectral gaps

By generalizing the path method, we show that nonlinear spectral gaps of a finite connected graph are uniformly bounded from below by a positive constant which is independent of the target metric space. We apply our result to an $r$-ball $T_{d,r}$ in the $d$-regular tree, and observe that the asymptotic behavior of nonlinear spectral gaps of $T_{d,r}$ as $r\to\infty$ does not depend on the target metric space, which is in contrast to the case of a sequence of expanders. We also apply our result to the $n$-dimensional Hamming cube $H_n$ and obtain an estimate of its nonlinear spectral gap with respect to an arbitrary metric space, which is asymptotically sharp as $n\to\infty$.Comment: to appear in Graphs and Combinatoric

Two-step regulation of trachealess ensures tight coupling of cell fate with morphogenesis in the Drosophila trachea

動物の発生において形と機能を調和させる仕組みを発見 --形の変化が細胞分化を方向づける--. 京都大学プレスリリース. 2019-08-28.During organogenesis, inductive signals cause cell differentiation and morphogenesis. However, how these phenomena are coordinated to form functional organs is poorly understood. Here, we show that cell differentiation of the Drosophila trachea is sequentially determined in two steps and that the second step is synchronous with the invagination of the epithelial sheet. The master gene trachealess is dispensable for the initiation of invagination, while it is essential for maintaining the invaginated structure, suggesting that tracheal morphogenesis and differentiation are separately induced. trachealess expression starts in bipotential tracheal/epidermal placode cells. After invagination, its expression is maintained in the invaginated cells but is extinguished in the remaining sheet cells. A trachealess cis-regulatory module that shows both tracheal enhancer activity and silencer activity in the surface epidermal sheet was identified. We propose that the coupling of trachealess expression with the invaginated structure ensures that only invaginated cells canalize robustly into the tracheal fate

Spatiotemporal remodeling of extracellular matrix orients epithelial sheet folding

細胞シートを3次元に折れたたむ仕組み発見 --接着素材の構築・解体が正確な生体組織の「折り紙」を実現--. 京都大学プレスリリース. 2023-09-04.Unveiling the mechanism of 3D folding of cell sheets: Constructing and disassembling adhesive materials for precise origami of tissues. 京都大学プレスリリース. 2023-09-07.Biological systems are inherently noisy; however, they produce highly stereotyped tissue morphology. Drosophila pupal wings show a highly stereotypic folding through uniform expansion and subsequent buckling of wing epithelium within a surrounding cuticle sac. The folding pattern produced by buckling is generally stochastic; it is thus unclear how buckling leads to stereotypic tissue folding of the wings. We found that the extracellular matrix (ECM) protein, Dumpy, guides the position and direction of buckling-induced folds. Dumpy anchors the wing epithelium to the overlying cuticle at specific tissue positions. Tissue-wide alterations of Dumpy deposition and degradation yielded different buckling patterns. In summary, we propose that spatiotemporal ECM remodeling shapes stereotyped tissue folding through dynamic interactions between the epithelium and its external structures

Single-cell transcriptome atlas of Drosophila gastrula 2.0

ショウジョウバエ原腸胚における1細胞遺伝子発現アトラスを作成 --ゲノム情報による発生制御の解明に向けた基盤的リソース--. 京都大学プレスリリース. 2023-07-11.During development, positional information directs cells to specific fates, leading them to differentiate with their own transcriptomes and express specific behaviors and functions. However, the mechanisms underlying these processes in a genome-wide view remain ambiguous, partly because the single-cell transcriptomic data of early developing embryos containing accurate spatial and lineage information are still lacking. Here, we report a single-cell transcriptome atlas of Drosophila gastrulae, divided into 77 transcriptomically distinct clusters. We find that the expression profiles of plasma-membrane-related genes, but not those of transcription-factor genes, represent each germ layer, supporting the nonequivalent contribution of each transcription-factor mRNA level to effector gene expression profiles at the transcriptome level. We also reconstruct the spatial expression patterns of all genes at the single-cell stripe level as the smallest unit. This atlas is an important resource for the genome-wide understanding of the mechanisms by which genes cooperatively orchestrate Drosophila gastrulation

Development of a new method for assessing otolith function in mice using three-dimensional binocular analysis of the otolith-ocular reflex

In the interaural direction, translational linear acceleration is loaded during lateral translational movement and gravitational acceleration is loaded during lateral tilting movement. These two types of acceleration induce eye movements via two kinds of otolith-ocular reflexes to compensate for movement and maintain clear vision: horizontal eye movement during translational movement, and torsional eye movement (torsion) during tilting movement. Although the two types of acceleration cannot be discriminated, the two otolith-ocular reflexes can distinguish them effectively. In the current study, we tested whether lateral-eyed mice exhibit both of these otolith-ocular reflexes. In addition, we propose a new index for assessing the otolith-ocular reflex in mice. During lateral translational movement, mice did not show appropriate horizontal eye movement, but exhibited unnecessary vertical torsion-like eye movement that compensated for the angle between the body axis and gravito-inertial acceleration (GIA; i.e., the sum of gravity and inertial force due to movement) by interpreting GIA as gravity. Using the new index (amplitude of vertical component of eye movement)/(angle between body axis and GIA), the mouse otolith-ocular reflex can be assessed without determining whether the otolith-ocular reflex is induced during translational movement or during tilting movement

CAT 0 クウカン ニ タイスル コテイテン セイシツ

京都大学0048新制・課程博士博士(理学)甲第12648号理博第3090号新制||理||1461(附属図書館)UT51-2006-U353京都大学大学院理学研究科数学・数理解析専攻(主査)教授 深谷 賢治, 教授 中島 啓, 教授 河野 明学位規則第4条第1項該当Doctor of ScienceKyoto UniversityDA

JNK and Yorkie drive tumor malignancy by inducing L-amino acid transporter 1 in Drosophila

Identifying a common oncogenesis pathway among tumors with different oncogenic mutations is critical for developing anti-cancer strategies. Here, we performed transcriptome analyses on two different models of Drosophila malignant tumors caused by Ras activation with cell polarity defects (RasV12/scrib-/-) or by microRNA bantam overexpression with endocytic defects (bantam/rab5-/-), followed by an RNAi screen for genes commonly essential for tumor growth and malignancy. We identified that Juvenile hormone Inducible-21 (JhI-21), a Drosophila homolog of the L-amino acid transporter 1 (LAT1), is upregulated in these malignant tumors with different oncogenic mutations and knocking down of JhI-21 strongly blocked their growth and invasion. JhI-21 expression was induced by simultaneous activation of c-Jun N-terminal kinase (JNK) and Yorkie (Yki) in these tumors and thereby contributed to tumor growth and progression by activating the mTOR-S6 pathway. Pharmacological inhibition of LAT1 activity in Drosophila larvae significantly suppressed growth of RasV12/scrib-/- tumors. Intriguingly, LAT1 inhibitory drugs did not suppress growth of bantam/rab5-/- tumors and overexpression of bantam rendered RasV12/scrib-/- tumors unresponsive to LAT1 inhibitors. Further analyses with RNA sequencing of bantam-expressing clones followed by an RNAi screen suggested that bantam induces drug resistance against LAT1 inhibitors via downregulation of the TMEM135-like gene CG31157. Our observations unveil an evolutionarily conserved role of LAT1 induction in driving Drosophila tumor malignancy and provide a powerful genetic model for studying cancer progression and drug resistance