Photobiomodulation therapy moderates cancer cachexia-associated muscle wasting through activating PI3K/AKT/FoxO3a pathway.

Cancer cachexia-associated muscle wasting as a multifactorial wasting syndrome, is an important factor affecting the long-term survival rate of tumor patients. Photobiomodulation therapy (PBMT) has emerged as a promising tool to cure and prevent many diseases. However, the effect of PBMT on skeletal muscle atrophy during cancer progression has not been fully demonstrated yet. Here, we found PBMT alleviated the atrophy of myotube diameter induced by cancer cells in vitro, and prevented cancer-associated muscle atrophy in mice bearing tumor. Mechanistically, the alleviation of muscle wasting by PBMT was found to be involved in inhibiting E3 ubiquitin ligases MAFbx and MuRF-1. In addition, transcriptomic analysis using RNA-seq and GSEA revealed that PI3K/AKT pathway might be involved in PBMT-prevented muscle cachexia. Next, we showed the protective effect of PBMT against muscle cachexia was totally blocked by AKT inhibitor in vitro and in vivo. Moreover, PBMT-activated AKT promoted FoxO3a phosphorylation and thus inhibiting the nucleus entry of FoxO3a. Lastly, in cisplatin-treated muscle cachexia model, PBMT had also been shown to ameliorate muscle atrophy through enhancing PI3K/AKT pathway to suppress MAFbx and MuRF-1 expression. These novel findings revealed that PBMT could be a promising therapeutic approach in treating muscle cachexia induced by cancer.

Construction and validation of a hypoxia-related gene signature to predict the prognosis of breast cancer.

BACKGROUND: Among the most common forms of cancer worldwide, breast cancer posed a serious threat to women. Recent research revealed a lack of oxygen, known as hypoxia, was crucial in forming breast cancer. This research aimed to create a robust signature with hypoxia-related genes to predict the prognosis of breast cancer patients. The function of hypoxia genes was further studied through cell line experiments. MATERIALS AND METHODS: In the bioinformatic part, transcriptome and clinical information of breast cancer were obtained from The Cancer Genome Atlas(TCGA). Hypoxia-related genes were downloaded from the Genecards Platform. Differentially expressed hypoxia-related genes (DEHRGs) were identified. The TCGA filtered data was evenly split, ensuring a 1:1 distribution between the training and testing sets. Prognostic-related DEHRGs were identified through Cox regression. The signature was established through the training set. Then, it was validated using the test set and external validation set GSE131769 from Gene Expression Omnibus (GEO). The nomogram was created by incorporating the signature and clinicopathological characteristics. The predictive value of the nomogram was evaluated by C-index and receiver operating characteristiccurve. Immune microenvironment and mutation burden were also examined. In the experiment part, the function of the two most significant hypoxia-related genes were further explored by cell-line experiments. RESULTS: In the bioinformatic part, 141 up-regulated and 157 down-regulated DEHRGs were screened out. A prognostic signature was constructed containing nine hypoxia genes (ALOX15B, CA9, CD24, CHEK1, FOXM1, HOTAIR, KCNJ11, NEDD9, PSME2) in the training set. Low-risk patients exhibited a much more favorable prognosis than higher-risk ones (P < 0.001). The signature was double-validated in the test set and GSE131769 (P = 0.006 and P = 0.001). The nomogram showed excellent predictive value with 1-year OS AUC: 0.788, 3-year OS AUC: 0.783, and 5-year OS AUC: 0.817. Patients in the high-risk group had a higher tumor mutation burden when compared to the low-risk group. In the experiment part, the down-regulation of PSME2 inhibited cell growth ability and clone formation capability of breast cancer cells, while the down-regulation of KCNJ11 did not have any functions. CONCLUSION: Based on 9 DEHRGs, a reliable signature was established through the bioinformatic method. It could accurately predict the prognosis of breast cancer patients. Cell line experiment indicated that PSME2 played a protective role. Summarily, we provided a new insight to predict the prognosis of breast cancer by hypoxia-related genes.

Tumor-associated macrophage subtypes on cancer immunity along with prognostic analysis and SPP1-mediated interactions between tumor cells and macrophages.

Tumor-associated macrophages (TAM) subtypes have been shown to impact cancer prognosis and resistance to immunotherapy. However, there is still a lack of systematic investigation into their molecular characteristics and clinical relevance in different cancer types. Single-cell RNA sequencing data from three different tumor types were used to cluster and type macrophages. Functional analysis and communication of TAM subpopulations were performed by Gene Ontology-Biological Process and CellChat respectively. Differential expression of characteristic genes in subpopulations was calculated using zscore as well as edgeR and Wilcoxon rank sum tests, and subsequently gene enrichment analysis of characteristic genes and anti-PD-1 resistance was performed by the REACTOME database. We revealed the heterogeneity of TAM, and identified eleven subtypes and their impact on prognosis. These subtypes expressed different molecular functions respectively, such as being involved in T cell activation, apoptosis and differentiation, or regulating viral bioprocesses or responses to viruses. The SPP1 pathway was identified as a critical mediator of communication between TAM subpopulations, as well as between TAM and epithelial cells. Macrophages with high expression of SPP1 resulted in poorer survival. By in vitro study, we showed SPP1 mediated the interactions between TAM clusters and between TAM and tumor cells. SPP1 promoted the tumor-promoting ability of TAM, and increased PDL1 expression and stemness of tumor cells. Inhibition of SPP1 attenuated N-cadherin and ß-catenin expression and the activation of AKT and STAT3 pathway in tumor cells. Additionally, we found that several subpopulations could decrease the sensitivity of anti-PD-1 therapy in melanoma. SPP1 signal was a critical pathway of communication between macrophage subtypes. Some specific macrophage subtypes were associated with immunotherapy resistance and prognosis in some cancer types.

[18F]AlF-ND-bisFAPI PET imaging of fibroblast activation protein as a biomarker to monitor the progression of liver fibrosis.

BACKGROUND: Hepatic fibrosis is a progressive disease, which is reversible in the early stages. The current monitoring methods have notable limitations that pose a challenge to early detection. In this study, we evaluated the utility of [18F]AlF-ND-bisFAPI positron emission tomography imaging of fibroblast activation protein (FAP) to monitor the progression of liver fibrosis. METHODS: Two mouse models of liver fibrosis were established by bile duct ligation and carbon tetrachloride administration, respectively. Positron emission tomography imaging was performed with the FAP-specific radiotracer [18F]AlF-ND-bisFAPI for the evaluation of rat HSCs and mouse models of fibrosis and combined with histopathology, immunohistochemical staining, and immunoblotting to elucidate the relationships among radioactivity uptake, FAP levels, and liver fibrosis progression. Furthermore, [18F]AlF-ND-bisFAPI autoradiography was performed to assess tracer binding in liver sections from patients with varying degrees of liver fibrosis. RESULTS: Cell experiments demonstrated that [18F]AlF-ND-bisFAPI uptake was specific in activated HSCs. Compared with control mice, [18F]AlF-ND-bisFAPI uptake in livers increased in the early stages of fibrosis and increased significantly further with disease progression. Immunohistochemistry and western blot analyses demonstrated that FAP expression increased with fibrosis severity. In accordance with the findings in animal models, ex vivo autoradiography on human fibrotic liver sections showed that radioactivity increased as fibrosis progressed from mild to severe. CONCLUSIONS: [18F]AlF-ND-bisFAPI positron emission tomography imaging is a promising noninvasive method for monitoring the progression of liver fibrosis.

The RNA sequencing results revealed the expression of different genes and signaling pathways during chemotherapy resistance in peripheral T-cell lymphoma.

BACKGROUND: Peripheral T-cell lymphoma (PTCL) is a subtype of non-Hodgkin's lymphoma that occurs primarily at extranodal sites and is commonly treated using chemotherapy and radiotherapy. PTCL is more malignant than other lymphoid tumors, resulting in a poor prognosis.The 5-year recurrence rate remains high, and there is a lack of standard treatment for patients with relapse-resistant disease. However, the molecular mechanisms underlying the resistance of peripheral T-cell lymphoma cells to chemotherapeutic drugs, as well as identifying strategies to overcome drug resistance remains unclear. In this study, we aimed to identify pivotal genes and signaling pathways associated with chemotherapy resistance in PTCL. METHODS: In this study, a total of 5 healthy controls and 7 clinical patients were enrolled; 4 patients were classified as chemotherapy sensitive, and 3 patients were classified as chemotherapy resistant. Peripheral blood samples were collected from each participant, and total RNA was extracted from the white blood cells. RNA sequencing was conducted on the Illumina HiSeq platform to obtain comprehensive gene expression profiles. Subsequently, the expression patterns of the DEGs associated with the most enriched signaling pathways, with a special focus on cancer-related genes, were validated using quantitative real-time polymerase chain reaction (qRT-PCR) in peripheral TCL patients. RESULTS: RNA sequencing (RNA-seq) analysis revealed 4063 differentially expressed genes (DEGs) in peripheral T-cell lymphoma specimens from patients with chemotherapy resistance, of which 1128 were upregulated and 2935 were downregulated. Subsequent quantitative gene expression analysis confirmed a differential expression pattern in all the libraries, with 9 downregulated genes and 10 upregulated genes validated through quantitative real-time PCR in 6 clinical specimens from patients with chemotherapy resistance. KEGG pathway analysis revealed significant alterations in several pathways, with 6 downregulated pathways and 9 upregulated pathways enriched in the DEGs. Notably, the TNF signaling pathway, which is extensively regulated, was among the pathways that exhibited significant changes. These findings suggest that DEGs and the TNF signaling pathway may play crucial roles in chemotherapy resistance in peripheral T-cell lymphoma. CONCLUSION: Our study revealed that the expression of specific genes, including TNFRSF1B, TRADD2, and MAP3K7, may play an important role in chemotherapy resistance in peripheral T-cell lymphoma. Moreover, we identified the downregulation of the TNF signaling pathway, a crucial pathway involved in cell survival, death, and differentiation, as a potential contributor to the development of chemotherapy resistance in peripheral T-cell lymphoma. These findings provide valuable insights into the molecular mechanisms underlying chemotherapy resistance and highlight potential targets for overcoming treatment resistance in this challenging disease.

Single-cell sequencing reveals the immune landscape of breast cancer patients with brain metastasis.

BACKGROUND: Breast cancer has the highest incidence rate of cancer worldwide, and brain metastases (BrM) are among the most malignant cases. While some patients have benefited from immune checkpoint inhibitors (ICIs), the complex anatomical structure of the brain and the heterogeneity of metastatic tumors have made it difficult to characterize the tumor immune microenvironment (TME) of metastatic tumors. METHODS: To address this, we used single-cell RNA sequencing (scRNA-seq) to analyze immune cells in the cerebrospinal fluid (CSF) of BrM patients with breast cancer, thereby providing a comprehensive view of the immune microenvironment landscape of BrM. RESULTS: Based on canonical marker genes, we identified nine cell types, and further identified their subtypes through differential expression gene (DEG) analysis. We compared the changes in cells and functions in the immune microenvironment of patients with different prognoses. Our analysis revealed a series of genes that promote tumor immune function (CCR5, LYZ, IGKC, MS4A1, etc.) and inhibit tumor immune function (SCGB2A2, CD24, etc.). CONCLUSIONS: The scRNA-seq in CSF provides a noninvasive method to describe the TME of breast cancer patients and guide immunotherapy.

Mapping of multiple neurotransmitter receptor subtypes and distinct protein complexes to the connectome.

Neurons express various combinations of neurotransmitter receptor (NR) subunits and receive inputs from multiple neuron types expressing different neurotransmitters. Localizing NR subunits to specific synaptic inputs has been challenging. Here, we use epitope-tagged endogenous NR subunits, expansion light-sheet microscopy, and electron microscopy (EM) connectomics to molecularly characterize synapses in Drosophila. We show that in directionally selective motion-sensitive neurons, different multiple NRs elaborated a highly stereotyped molecular topography with NR localized to specific domains receiving cell-type-specific inputs. Developmental studies suggested that NRs or complexes of them with other membrane proteins determine patterns of synaptic inputs. In support of this model, we identify a transmembrane protein selectively associated with a subset of spatially restricted synapses and demonstrate its requirement for synapse formation through genetic analysis. We propose that mechanisms that regulate the precise spatial distribution of NRs provide a molecular cartography specifying the patterns of synaptic connections onto dendrites.

Unified 3D and 4D Panoptic Segmentation via Dynamic Shifting Networks.

With the rapid advances in autonomous driving, it becomes critical to equip its sensing system with more holistic 3D perception. However, widely explored tasks like 3D detection or point cloud semantic segmentation focus on parsing either the objects or scenes. In this work, we propose to address the challenging task of LiDAR-based Panoptic Segmentation, which aims to parse both objects and scenes in a unified manner. In particular, we propose Dynamic Shifting Network (DS-Net), which serves as an effective panoptic segmentation framework in the point cloud realm. DS-Net features a dynamic shifting module for complex LiDAR point cloud distributions. We present an efficient learnable clustering module, dynamic shifting, which adapts kernel functions for different instances. To further explore the temporal information, we extend the single-scan processing framework to its temporal version, 4D-DS-Net, for the task of 4D Panoptic Segmentation, where the same instance across multiple frames should be given the same ID prediction. Instead of naively appending a tracking module to DS-Net, we propose to solve the 4D panoptic segmentation in a more unified way. Specifically, 4D-DS-Net first constructs 4D data volume by aligning consecutive LiDAR scans, upon which the temporally unified instance clustering is performed to obtain the final results. Extensive experiments on two large-scale autonomous driving LiDAR datasets, SemanticKITTI and Panoptic nuScenes, are conducted to demonstrate the effectiveness and superior performance of the proposed solution.

Expression of PD-1 mitigates phagocytic activities TAM in osteosarcoma.

The high expression of programmed death 1 (PD-1) is a hallmark of T cell exhaustion, consequently inhibiting the anti-tumor immunity, tumor-associated macrophages (TAMs) aggravate Osteosarcoma (OS) progression. However, PD-1 expression on TAMs in OS metastasis remains unclear. Here, we used scRNA-Seq of 15500 individual cells from human OS lung metastatic lesion, identified thirteen major cell clusters. Our data revealed that tumor-infiltrating lymphocytes (TILs) OS lung metastatic accompanied by accumulation of exhausted T cells and regulatory T cells (Tregs). CD3+ T cells from human OS lung metastatic exhibited lower proliferation than in primary tissue. Importantly, TAMs mainly comprise immunosuppressive M2 phenotype in OS metastasis. Mechanistically, we found that PD-1 of TAMs inhibits the phagocytic potency, further promoting the progression of OS metastasis. Therefore, the study provides a strong technical support for OS immunotherapy based on PD-1 inhibitors.

RNNPose: 6-DoF Object Pose Estimation Via Recurrent Correspondence Field Estimation and Pose Optimization.

6-DoF object pose estimation from a monocular image is a challenging problem, where a post-refinement procedure is generally needed for high-precision estimation. In this paper, we propose a framework, dubbed RNNPose, based on a recurrent neural network (RNN) for object pose refinement, which is robust to erroneous initial poses and occlusions. During the recurrent iterations, object pose refinement is formulated as a non-linear least squares problem based on the estimated correspondence field (between a rendered image and the observed image). The problem is then solved by a differentiable Levenberg-Marquardt (LM) algorithm enabling end-to-end training. The correspondence field estimation and pose refinement are conducted alternately in each iteration to improve the object poses. Furthermore, to improve the robustness against occlusion, we introduce a consistency-check mechanism based on the learned descriptors of the 3D model and observed 2D images, which downweights the unreliable correspondences during pose optimization. We evaluate RNNPose on several public datasets, including LINEMOD, Occlusion-LINEMOD, YCB-Video and TLESS. We demonstrate state-of-the-art performance and strong robustness against severe clutter and occlusion in the scenes. Extensive experiments validate the effectiveness of our proposed method. Besides, the extended system based on RNNPose successfully generalizes to multi-instance scenarios and achieves top-tier performance on the TLESS dataset.

M6A demethylase ALKBH5 regulates FOXO1 mRNA stability and chemoresistance in triple-negative breast cancer.

Resistance to chemotherapy is the main reason for treatment failure and poor prognosis in patients with triple-negative breast cancer (TNBC). Although the association of RNA N6-methyladenosine (m6A) modifications with therapy resistance is noticed, its role in the development of therapeutic resistance in TNBC is not well documented. This study aimed to investigate the potential mechanisms underlying reactive oxygen species (ROS) regulation in doxorubicin (DOX)-resistant TNBC. Here, we found that DOX-resistant TNBC cells displayed low ROS levels because of increased expression of superoxide dismutase (SOD2), thus maintaining cancer stem cells (CSCs) characteristics and DOX resistance. FOXO1 is a master regulator that reduces cellular ROS in DOX-resistant TNBC cells, and knockdown of FOXO1 significantly increased ROS levels by inhibiting SOD2 expression. Moreover, the m6A demethylase ALKBH5 promoted m6A demethylation of FOXO1 mRNA and increased FOXO1 mRNA stability in DOX-resistant TNBC cells. The analysis of clinical samples revealed that the increased expression levels of ALKBH5, FOXO1, and SOD2 were significantly positively correlated with chemoresistance and poor prognosis in patients with TNBC. To our knowledge, this is the first study to highlight that ALKBH5-mediated FOXO1 mRNA demethylation contributes to CSCs characteristics and DOX resistance in TNBC cells. Furthermore, pharmacological targeting of FOXO1 profoundly restored the response of DOX-resistant TNBC cells, both in vitro and in vivo. In conclusion, we demonstrated a critical function of ALKBH5-mediated m6A demethylation of FOXO1 mRNA in restoring redox balance, which in turn promoting CSCs characteristics and DOX resistance in TNBC, and suggested that targeting the ALKBH5/FOXO1 axis has therapeutic potential for patients with TNBC refractory to chemotherapy.

CGOF++: Controllable 3D Face Synthesis With Conditional Generative Occupancy Fields.

Capitalizing on the recent advances in image generation models, existing controllable face image synthesis methods are able to generate high-fidelity images with some levels of controllability, e.g., controlling the shapes, expressions, textures, and poses of the generated face images. However, previous methods focus on controllable 2D image generative models, which are prone to producing inconsistent face images under large expression and pose changes. In this paper, we propose a new NeRF-based conditional 3D face synthesis framework, which enables 3D controllability over the generated face images by imposing explicit 3D conditions from 3D face priors. At its core is a conditional Generative Occupancy Field (cGOF++) that effectively enforces the shape of the generated face to conform to a given 3D Morphable Model (3DMM) mesh, built on top of EG3D (Chan et al. 2022), a recent tri-plane-based generative model. To achieve accurate control over fine-grained 3D face shapes of the synthesized images, we additionally incorporate a 3D landmark loss as well as a volume warping loss into our synthesis framework. Experiments validate the effectiveness of the proposed method, which is able to generate high-fidelity face images and shows more precise 3D controllability than state-of-the-art 2D-based controllable face synthesis methods.

177Lu-Labeled Bivalent Ligands of Prostate-Specific Membrane Antigen for Endoradiotherapy of Prostate Cancer.

Recently, we developed a bivalent prostate-specific membrane antigen (PSMA) radioligand ([18F]AlF-Bi-PSMA), which showed higher tumor uptake and retention in PSMA-positive mouse models than the clinically used radioligands, [68Ga]Ga-PSMA-11 and [18F]PSMA-1007. Here, we developed two 177Lu-labeled bivalent PSMA ligands with (DOTA-Alb-Bi-PSMA) or without an albumin-binding motif (DOTA-Bi-PSMA) to enhance radiotherapeutic efficacy with minimal toxicity. The results demonstrated that both 177Lu-labeled bivalent radioligands showed good stability, high binding affinity, and PSMA-targeting specificity in vitro. Compared with [177Lu]Lu-PSMA-617, both [177Lu]Lu-Bi-PSMA and [177Lu]Lu-Alb-Bi-PSMA showed a higher area under the curve (AUC) of tumor accumulation and superior therapeutic efficacy. However, [177Lu]Lu-Alb-Bi-PSMA exhibited a dose-dependent increase in acute damage to kidneys. In terms of the radionuclide therapy efficacy and side effects, [177Lu]Lu-Bi-PSMA exhibited well-balanced action with high tumor-to-organs AUC ratios, resulting in remarkable therapeutic efficacy and negligible side effects. These promising results warrant further investigations to achieve the clinical translation of [177Lu]Lu-Bi-PSMA.

The Improved Method for Indoor 3D Pedestrian Positioning Based on Dual Foot-Mounted IMU System.

Micro-Electro-Mechanical System (MEMS) inertial sensors, characterized by their small size, low cost, and low power consumption, are commonly used in foot-mounted wearable pedestrian autonomous positioning systems. However, they also have drawbacks such as heading drift and poor repeatability. To address these issues, this paper proposes an improved pedestrian autonomous 3D positioning algorithm based on dual-foot motion characteristic constraints. Two sets of small-sized Inertial Measurement Units (IMU) are worn on the left and right feet of pedestrians to form an autonomous positioning system, each integrated with low-cost, low-power micro-inertial sensor chips. On the one hand, an improved adaptive zero-velocity detection algorithm is employed to enhance discrimination accuracy under different step-speed conditions. On the other hand, considering the dual-foot gait characteristics and the height difference feature during stair ascent and descent, horizontal position update algorithms based on dual-foot motion trajectory constraints and height update algorithms based on dual-foot height differences are, respectively, designed. These algorithms aim to re-correct the pedestrian position information updated at zero velocity in both horizontal and vertical directions. The experimental results indicate that in a laboratory environment, the 3D positioning error is reduced by 93.9% compared to unconstrained conditions. Simultaneously, the proposed approach enhances the accuracy, continuity, and repeatability of the foot-mounted IMU positioning system without the need for additional power consumption.

Corrigendum: The development of microscopic imaging technology and its application in micro-and nanotechnology.

[This corrects the article DOI: 10.3389/fchem.2022.931169.].

Corrigendum: Detection methods of nanoparticles synthesized by gas-phase method: a review.

[This corrects the article DOI: 10.3389/fchem.2022.845363.].

Discovery of 5-(Pyrimidin-2-ylamino)-1H-indole-2-carboxamide Derivatives as Nur77 Modulators with Selective and Potent Activity Against Triple-Negative Breast Cancer.

The orphan nuclear receptor Nur77 has been validated as a potential drug target for treating breast cancer. Therefore, focusing on the SAR study of the lead 8b (KDSPR(Nur77) = 354 nM), we found the active compound ja which exhibited improved Nur77-binding capability (KDSPR(Nur77) = 91 nM) and excellent antiproliferative activities against breast cancer cell lines. Interestingly, ja acted as a potent and selective Nur77 antagonist, displaying good potency against triple-negative breast cancer (TNBC) cell lines but did not inhibit human normal breast cancer cell line MCF-10A (SI > 20). Exceptionally, ja Nur77-dependently caused mitochondria dysfunction and induced the caspase-dependent apoptosis by mediating the TP53 phosphorylation pathway. Moreover, ja significantly suppressed MDA-MB-231 xenograft tumor growth but had no apparent side effects in mice and zebrafish. Overall, ja demonstrated to be the first Nur77 modulator mediating the TP53 phosphorylation pathway that has the potential as a novel anticancer agent for TNBC.

Cerebral Abscess Infected by Nocardia gipuzkoensis.

Purpose: Nocardia gipuzkoensis is a novel species that solely identified in patients with pulmonary infections by far. Growing evidence showed the excellent performance of metagenomics next-generation sequencing (mNGS) on pathogenic identification, especially for new species. Here, we described the first case of an elderly female patient suddenly suffering from neurological disorders owing to N. gipuzkoensis infection. And linezolid could effectively treat N. gipuzkoensis infection. Patients and Methods: The results of imaging, laboratory cultures, and mNGS, as well as therapeutic process are shared. Results: An elderly female patient suddenly suffered from neurological disorders with dysphasia and right limb trembles under no obvious causes. Subsequently, she was diagnosed as intracranial space-occupying lesions by magnetic resonance imaging (MRI). The isolate from brain secretion was further identified as N. gipuzkoensis through mNGS. The targeted therapy with linezolid according to the antimicrobial susceptibility was used to treat cerebral abscess induced by N. gipuzkoensis. During the follow-up, no relapse was observed for the patient after surgery for 104 days. Conclusion: Cerebral abscess induced by N. gipuzkoensis is rare disorder with high mortality. mNGS has been identified as a promising tool in pathogen diagnosis for timely therapy. Linezolid as one of the antimicrobial drugs could effectively treat N. gipuzkoensis infection and prevent adverse outcomes.

Mapping of multiple neurotransmitter receptor subtypes and distinct protein complexes to the connectome.

Neurons express different combinations of neurotransmitter receptor (NR) subunits and receive inputs from multiple neuron types expressing different neurotransmitters. Localizing NR subunits to specific synaptic inputs has been challenging. Here we use epitope tagged endogenous NR subunits, expansion light-sheet microscopy, and EM connectomics to molecularly characterize synapses in Drosophila. We show that in directionally selective motion sensitive neurons, different multiple NRs elaborated a highly stereotyped molecular topography with NR localized to specific domains receiving cell-type specific inputs. Developmental studies suggested that NRs or complexes of them with other membrane proteins determines patterns of synaptic inputs. In support of this model, we identify a transmembrane protein associated selectively with a subset of spatially restricted synapses and demonstrate through genetic analysis its requirement for synapse formation. We propose that mechanisms which regulate the precise spatial distribution of NRs provide a molecular cartography specifying the patterns of synaptic connections onto dendrites.