Review
Cell Biology
S. Jain, S. L. Zipursky
Summary: Wiring an animal brain is a complex process that requires precise timing and coordination of genetic programs across different cell types. In this review, the temporal regulators of wiring programs and their control over time and space are discussed. These temporal regulators are induced by cell-extrinsic cues and control cell-type specific transcription factors, which determine the target specificity of wiring programs. Understanding these temporal regulators will be crucial for uncovering the mechanisms underlying brain wiring and developing in vitro models like brain organoids.
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2023)
Editorial Material
Biochemistry & Molecular Biology
Joachim Fuchs, P. Robin Hiesinger
Summary: Recent electron microscopy-based connectomes of the Caenorhabditis elegans nervous system allow for testing classic models for brain wiring development. Statistical analyses show that neuronal adjacencies (the contactome) can partially predict synaptic connectivity (the connectome).
Editorial Material
Neurosciences
Andrew Kovalenko, Avraham Yaron
Summary: This article investigates the role and regulatory mechanisms of transcription factors in the nervous system, revealing a new level of complexity.
Article
Biochemistry & Molecular Biology
Juyoun Yoo, Mark Dombrovski, Parmis Mirshahidi, Aljoscha Nern, Samuel A. Locascio, S. Lawrence Zipursky, Yerbol Z. Kurmangaliyev
Summary: Advances in brain connectomics have revealed the complexity of neural circuits. This study integrated the synapse-level connectome with developmental expression patterns and binding specificities of cell adhesion molecules to understand the wiring specificity in the Drosophila visual system. They found that specific receptor-ligand pairs play a crucial role in synaptic localization and connections.
Article
Multidisciplinary Sciences
Mehmet Neset Ozel, Claudia Skok Gibbs, Isabel Holguera, Mennah Soliman, Richard Bonneau, Claude Desplan
Summary: The study reveals that the Drosophila visual system contains nearly 200 distinct types of neurons, each defined by unique combinations of about 10 continuously expressed transcription factors. Modifying the terminal selector code can predictably convert neuronal fates and these conversions are morphologically and transcriptionally complete. Additionally, the study identifies one gene that is linked to an upstream patterning factor, which specifies neuronal fates in stem cells.
Article
Neurosciences
Gabriela Edwards-Faret, Filip de Vin, Michal Slezak, Lennart Gollenbeck, Ruchan Karaman, Yohei Shinmyo, Mykhailo Y. Batiuk, Carmen Menacho Pando, Johann Urschitz, Melvin Y. Rincon, Stefan Moisyadi, Frank Schnuetgen, Hiroshi Kawasaki, Dietmar Schmucker, Matthew G. Holt
Summary: Single-cell sequencing has identified numerous genes expressed in different cell types and model organisms. The nervous system, in particular, contains many understudied interacting cell types. Future experiments on gene function are crucial to understanding their roles in diverse cellular and evolutionary contexts but are often limited by technical constraints in non-genetic animal systems.
Review
Anatomy & Morphology
Elena Cortes, Joseph S. Pak, Engin Ozkan
Summary: The map of connections is a fundamental property of a neuronal circuit. Neuronal surface receptors and their interactions with other receptors, ligands, and matrix molecules play crucial roles in the growth of axons and dendrites, selection of synaptic targets, and formation of functional synapses. The spatiotemporal regulation of these receptors and cues allows for specificity in the developmental pathways that wire stereotyped circuits. The conservation of molecular families controlling axon guidance and synapse formation is generally observed across animals, but there are exceptions that have important consequences for neuronal connectivity.
DEVELOPMENTAL DYNAMICS
(2023)
Review
Neurosciences
Qiang Wu, Zhilian Jia
Summary: There are over a thousand trillion specific synaptic connections in the human brain, with clustered Pcdh genes being crucial for neuronal identity codes. These genes generate a vast number of diverse cell-surface Pcdhs through 3-D architectural and biophysical mechanisms as neural codes in the brain.
NEUROSCIENCE BULLETIN
(2021)
Article
Biochemistry & Molecular Biology
Haiyang Dong, Pengjuan Guo, Jian Zhang, Lili Wu, Ying Fu, Lei Li, Yanda Zhu, Yiwen Du, Jilong Shi, Shixin Zhang, Guo Li, Bingbing Xu, Lina Bian, Xiaohua Zhu, Wendong You, Feng Shi, Xiaofeng Yang, Jianhua Huang, Yongfeng Jin
Summary: Alternative splicing of Drosophila Dscam1 into a large number of isoforms provides a unique molecular code for neuronal self-recognition and self-avoidance. However, expressing only a single isoform leads to abnormal growth and segregation defects in axonal branches, suggesting a functional link between Dscam1 expression levels and isoform diversity.
Article
Developmental Biology
Samantha E. Galindo, Abby J. Wood, Patricia C. Cooney, Luke A. Hammond, Wesley B. Grueber
Summary: Synaptic connections play important roles in information processing within neurons and their precise subcellular localization is crucial for this process. In this study, we investigated the role of axon-axon interactions in the precise targeting and subcellular wiring of the Drosophila somatosensory circuitry. We found that nociceptive and gentle touch neurons form non-overlapping layers in the central nervous system, and their axons synapse onto distinct dendritic regions of a second-order interneuron, resulting in touch-specific and nociceptive-specific connectivity. Our findings suggest that axon-axon interactions and modality-specific timing of axon targeting are key factors in determining the subcellular connection specificity of somatosensory circuitry.
Article
Multidisciplinary Sciences
Saroor A. Patel, Shoko Hirosue, Paulo Rodrigues, Erika Vojtasova, Emma K. Richardson, Jianfeng Ge, Saiful E. Syafruddin, Alyson Speed, Evangelia K. Papachristou, David Baker, David Clarke, Stephenie Purvis, Ludovic Wesolowski, Anna Dyas, Leticia Castillon, Veronica Caraffini, Dora Bihary, Cissy Yong, David J. Harrison, Grant D. Stewart, Mitchell J. Machiela, Mark P. Purdue, Stephen J. Chanock, Anne Y. Warren, Shamith A. Samarajiwa, Jason S. Carroll, Sakari Vanharanta
Summary: Using experimental models and analysis of patient samples, researchers have demonstrated that the transcription factor PAX8 is essential for oncogenic signaling and plays a key role in two common genetic alterations associated with ccRCC.
Article
Biology
Mohanakarthik P. Nallasivan, Irmgard U. Haussmann, Alberto Civetta, Matthias Soller
Summary: The study identified the nuclear pore protein Nup54 gene as crucial for the sex peptide response in female Drosophila, influencing neuronal wiring and sexual differentiation. Mutations in Nup54 resulted in the inability to lay eggs and reduced receptivity after exposure to sex peptide, highlighting its role in regulating post-mating behaviors. This suggests a link between nuclear pore functionality and the neuronal responses to male-derived sex peptide, shedding light on the underlying mechanisms of sexual conflict in fruit flies.
Article
Cell Biology
Weiling Hong, Jian Zhang, Haiyang Dong, Yang Shi, Hongru Ma, Fengyan Zhou, Bingbing Xu, Ying Fu, Shixin Zhang, Shouqing Hou, Guo Li, Yandan Wu, Shuo Chen, Xiaohua Zhu, Wendong You, Feng Shi, Xiaofeng Yang, Zhefeng Gong, Jianhua Huang, Yongfeng Jin
Summary: The study provides evidence that splicing bias of Drosophila Dscam1 is crucial for the axonal wiring of mushroom bodies, with different bias types influencing development and non-repulsive signaling of MB.
Review
Biochemistry & Molecular Biology
Stefanie A. I. Weiss, Salome R. T. Rehm, Natascha C. Perera, Martin L. Biniossek, Oliver Schilling, Dieter E. Jenne
Summary: The deepest evolutionary branches of the trypsin/chymotrypsin family of serine proteases are represented by digestive enzymes in the gastrointestinal tract and multi-domain proteases in the blood coagulation and complement system. The immune defense system in vertebrates has developed diverse cleavage specificities similar to the ancient digestive system. Neutrophil serine proteases (NSPs) have a broad range of specificities and trace their origin back to a circulating liver-derived trypsin-like protease. These serine proteases are produced in precursor cells in the bone marrow and safely stored in granules in circulating neutrophils, with their actions tightly controlled by various factors such as recruitment and activation of neutrophils and soluble inhibitors in different body fluids. The high structural plasticity of the trypsin fold has enabled an extraordinary dynamic range and rapid defense responses.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
P. Robin Hiesinger
Summary: The essay explores the continuum of actions from permissive to instructive factors in molecular mechanisms that guide axons or specify synaptic contacts. It suggests that a composite of seemingly permissive factors can define a specific instruction even without a dominant contributor, and individual factors may not be intuitively related to the overall instruction or phenotypic outcome.
Article
Neurosciences
Yukari H. Takeo, S. Andrew Shuster, Linnie Jiang, Miley C. Hu, David J. Luginbuhl, Thomas Rulicke, Ximena Contreras, Simon Hippenmeyer, Mark J. Wagner, Surya Ganguli, Liqun Luo
Summary: The study demonstrates that sparse knockout of GluD2 in the cerebellar cortex leads to abnormal dendrite development in Purkinje cells, due to a deficit in competitive interactions dependent on Cbln1/GluD2. A generative model based on competitive synaptogenesis replicates these phenotypes.
Article
Neurosciences
Qijing Xie, Jiefu Li, Hongjie Li, Namrata D. Udeshi, Tanya Svinkina, Daniel Orlin, Sayeh Kohani, Ricardo Guajardo, D. R. Mani, Chuanyun Xu, Tongchao Li, Shuo Han, Wei Wei, S. Andrew Shuster, David J. Luginbuhl, Stephen R. Quake, Swetha E. Murthy, Alice Y. Ting, Steven A. Carr, Liqun Luo
Summary: The transcription factor Acj6 regulates the precise dendrite targeting of Drosophila olfactory projection neurons by controlling the expression of cell-surface proteins. This study identifies specific cell-surface proteins that execute Acj6-regulated wiring decisions and demonstrates that Acj6 employs unique sets of these proteins in different neuron types for dendrite targeting. The combined expression of these proteins effectively rescues mutant phenotypes, highlighting the importance of Acj6 in controlling wiring specificity.
Article
Multidisciplinary Sciences
Hongjie Li, Jasper Janssens, Maxime De Waegeneer, Sai Saroja Kolluru, Kristofer Davie, Vincent Gardeux, Wouter Saelens, Fabrice David, Maria Brbic, Jure Leskovec, Colleen N. McLaughlin, Qijing Xie, Robert C. Jones, Katja Brueckner, Jiwon Shim, Sudhir Gopal Tattikota, Frank Schnorrer, Katja Rust, Todd G. Nystul, Zita Carvalho-Santos, Carlos Ribeiro, Soumitra Pal, Sharvani Mahadevaraju, Teresa M. Przytycka, Aaron M. Allen, Stephen F. Goodwin, Cameron W. Berry, Margaret T. Fuller, Helen White-Cooper, Erika L. Matunis, Stephen DiNardo, Anthony Galenza, Lucy Erin O'Brien, Julian A. T. Dow, Heinrich Jasper, Brian Oliver, Norbert Perrimon, Bart Deplancke, Stephen R. Quake, Liqun Luo, Stein Aerts
Summary: This study presents a single-cell atlas of the fruit fly Drosophila melanogaster, including 580,000 nuclei and annotations of over 250 distinct cell types. It serves as a valuable resource for the Drosophila community and provides a reference for studying genetic perturbations and disease models at single-cell resolution.
Article
Multidisciplinary Sciences
Jessica A. Osterhout, Vikrant Kapoor, Stephen W. Eichhorn, Eric Vaughn, Jeffrey D. Moore, Ding Liu, Dean Lee, Laura A. DeNardo, Liqun Luo, Xiaowei Zhuang, Catherine Dulac
Summary: This study identifies a previously uncharacterized population of neurons in the brain that are activated after infection, playing a crucial role in generating fever response and other sickness symptoms. By examining gene expression and electrophysiological measurements, the researchers uncover a mechanism where these neurons are influenced by immune signals released by non-neuronal cells during infection and are functionally connected to brain areas controlling body temperature and appetite.
Editorial Material
Neurosciences
Jalal Baruni, Liqun Luo
Summary: In this study, Paquelet et al. utilize microendoscopy to record the activity of over 2,000 dorsal raphe serotonin neurons, providing new insights into their function at both the level of individual neurons and the population.
Article
Multidisciplinary Sciences
Jun Xu, Yifang Liu, Hongjie Li, Alexander J. Tarashansky, Colin H. Kalicki, Ruei-Jiun Hung, Yanhui Hu, Aram Comjean, Sai Saroja Kolluru, Bo Wang, Stephen R. Quake, Liqun Luo, Andrew P. McMahon, Julian A. T. Dow, Norbert Perrimon
Summary: The single-nucleus study of the Drosophila renal system identified various cell types and their roles in kidney function and regeneration, providing insights for the generation of disease models.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Editorial Material
Biochemistry & Molecular Biology
Colleen N. McLaughlin, Liqun Luo
Summary: In this article, the authors reveal that mosquitoes' strong attraction to humans may be attributed to non-canonical olfactory circuit organization and coding, which enables them to locate human hosts effectively.
Article
Neurosciences
S. Andrew Shuster, Jiefu Li, URee Chon, Miley C. Sinantha-Hu, David J. Luginbuhl, Namrata D. Udeshi, Dominique Kiki Carey, Yukari H. Takeo, Qijing Xie, Chuanyun Xu, D. R. Mani, Shuo Han, Alice Y. Ting, Steven A. Carr, Liqun Luo
Summary: A new method called iPEEL was developed to identify cell-surface proteomes in specific cell types in their native tissues. By applying iPEEL to studying developing and mature cerebellar Purkinje cells, researchers discovered differential enrichment in cell-surface proteomes with post-translational protein processing and synaptic functions in these cells. They also identified the critical role of Armh4 in Purkinje cell dendrite morphogenesis through in vivo loss-of-function screening. Disrupting Armh4's endocytosis augmented its effect on dendrite morphogenesis. This study highlights the importance of CSP profiling in native mammalian tissues for understanding cell-surface signaling regulations.
Article
Multidisciplinary Sciences
Ya-Ting Chang, Max Kowalczyk, P. Michelle Fogerson, Yu-Ju Lee, Minza Haque, Eliza L. Adams, David C. Wang, Laura A. DeNardo, Marc Tessier-Lavigne, John R. Huguenard, Liqun Luo, Wei-Hsiang Huang
Summary: Hyperexcitability of brain circuits is a common feature of autism spectrum disorders. This study identifies Rai1 as a negative regulator of excitability, and its deletion results in increased seizure susceptibility and prolonged hippocampal seizure duration.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Taehong Yang, Daniel W. Bayless, Yichao Wei, Dan Landayan, Ivo M. Marcelo, Yangpeng Wang, Laura A. DeNardo, Liqun Luo, Shaul Druckmann, Nirao M. Shah
Summary: Social interactions rely on the awareness and understanding of others' behavior. Mirror neurons, which represent actions of self and others, are crucial for this cognitive process. In this study, we identified mirror neurons in the hypothalamus of mice and found that their activity is essential for aggression and can even trigger aggressive displays towards mirror images.
Article
Biochemical Research Methods
Yuhang Fan, Zaneta Andrusivova, Yunming Wu, Chew Chai, Ludvig Larsson, Mengxiao He, Liqun Luo, Joakim Lundeberg, Bo Wang
Summary: Expansion spatial transcriptomics (Ex-ST) combines tissue expansion and an improved RNA capture protocol to achieve high spatial resolution in array-based spatial transcriptomics. By clearing and expanding tissue before capturing the entire polyadenylated transcriptome, Ex-ST overcomes the limitation of array density. We demonstrate its effectiveness using mouse brain samples.
Article
Multidisciplinary Sciences
Tzu-Chiao Lu, Maria Brbic, Ye-Jin Park, Tyler Jackson, Jiaye Chen, Sai Saroja Kolluru, Yanyan Qi, Nadja Sandra Katheder, Xiaoyu Tracy Cai, Seungjae Lee, Yen -Chung Chen, Niccole Auld, Chung-Yi Liang, Sophia H. Ding, Doug Welsch, Samuel D'Souza, Angela Oliveira Pisco, Robert C. Jones, Jure Leskovec, Eric C. Lai, Hugo J. Bellen, Liqun Luo, Heinrich Jasper, Stephen R. Quake, Hongjie Li
Summary: This study presents the Aging Fly Cell Atlas, which is a single-nucleus transcriptomic map of the whole aging Drosophila. It reveals changes in tissue cell composition, gene expression, and cell identities during aging, and develops aging clock models that predict fly age based on ribosomal gene expression. The atlas provides a valuable resource for studying fundamental principles of aging in complex organisms.
Article
Biochemistry & Molecular Biology
Daniel W. Bayless, Chung-ha O. Davis, Renzhi Yang, Yichao Wei, Vinicius Miessler de Andrade Carvalho, Joseph R. Knoedler, Taehong Yang, Oscar Livingston, Akira Lomvardas, Gabriela J. Martins, Ana Mafalda Vicente, Jun B. Ding, Liqun Luo, Nirao M. Shash
Summary: This study has identified a neural circuit that governs key aspects of innate male sexual behavior, including motor displays, drive, and reward. This circuit connects chemosensory input to neurons that regulate motor output and reward centers.
Article
Multidisciplinary Sciences
Ya-Hui Chou, Chi-Jen Yang, Hao-Wei Huang, Nan-Fu Liou, Michael Raphael Panganiban, David Luginbuhl, Yijie Yin, Istvan Taisz, Liang Liang, Gregory S. X. E. Jefferis, Liqun Luo
Summary: In this study, the authors used genetic labeling and electron microscopy connectomics to investigate the variability of a specific neuron, TC-LN, in its innervation patterns. They found that this neuron exhibits extraordinary variability and that it is influenced by factors such as sex, courtship experience, and mating in relation to food intake. The researchers propose that this mating-associated variability regulates how food odor is interpreted by the inhibitory network to modulate feeding behavior.
