Biology subjects

Muotri, A. R.

Publications and source records attributed to Muotri, A. R..

At least 19 recordsLinked to original sources

bioRxiv2026

SETD5 dysfunction in human astrocytes drives IL-6-mediated neuronal impairments via the JAK/STAT signaling pathway

Intellectual disability (ID) and autism spectrum disorder (ASD) are neurodevelopmental conditions marked by lifelong impairments in cognitive, motor, and social functions. Hundreds of genetic variants have been linked to these disorders, including mutations in chromatin regulators such as the SET-domain-containing protein 5 (SETD5) gene. Most studies linking SETD5 loss-of-function to ASD/ID have focused primarily on neurons. However, while SETD5 is highly expressed in astrocytes, its role in glia cells remains poorly understood. Here, we examine how dysfunction of SETD5 in human-induced pluripotent stem cell (hiPSC)-derived astrocytes affects neuronal physiology. We show that SETD5-deficient astrocytes have increased levels of extracellular reactive oxygen species (ROS), glutamate, and interleukins-6 and 8 (IL-6 and IL-8). Elevated astrocytic IL-6 exerts a non-cell autonomous harmful effect on healthy neurons. Using SETD5-deficient astrocytes as a screening platform, we identify the JAK/STAT pathway as an upstream regulator of abnormal IL-6 accumulation associated with SETD5 dysfunction. Accordingly, pharmacological inhibition of JAK-STAT signaling restores extracellular IL-6 to basal levels and partially rescues astrocyte morphology and neuronal deficits. Collectively, these findings highlight the JAK/STAT pathway as a key regulator of SETD5-mediated astrocytic function and suggest its potential as a therapeutic target for astrocytic-driven neuronal impairments in ASD and ID.

neuroscience↗

bioRxiv2025

A neurorecording toolkit for longitudinal assessments of transplanted human cortical organoids in vivo

Human cortical organoids (hCOs) are three-dimensional neural cell aggregates that recapitulate certain structural and functional aspects of the developing human cortex. Xenotransplantation of hCOs into the rodent brain enables human-centric modeling of neurodevelopmental processes in a physiologically relevant environment. Here, we present a neurorecording toolkit for longitudinal structural and functional assessment of hCO xenografts as they mature in vivo. Single hCOs were implanted into the retrosplenial cortex of adult immunodeficient mice and monitored for up to 8 months. Optical coherence tomography was used for label-free imaging of xenograft vascularization and structure, enabling quantitative assessments of capillary density and graft volume. To probe neuronal activity, human neurons were labeled with a calcium sensor before implantation using either adeno-associated or lentivirus for sparse or dense neuronal labeling, respectively. Fluorescent imaging was conducted using two-photon, widefield, and swept confocally-aligned planar excitation microscopy for single cell, whole-graft, and volumetric calcium imaging, respectively. Results from these modalities indicate an increase in neuronal activity and synchronicity over time during in vivo graft maturation. Further, we chronically implanted surface graphene microelectrode arrays (gMEAs) and performed recordings of xenograft and host local field potential signals simultaneously with 2P calcium imaging, confirming the spatial localization and human origin of electrical signals recorded at the xenograft surface.

neuroscience↗

bioRxiv2025

Large-scale discovery of neural enhancers for cis-regulation therapies

CRISPR-based gene activation (CRISPRa) has emerged as a promising therapeutic approach for neurodevelopmental disorders (NDD) caused by haploinsufficiency. However, scaling this cis-regulatory therapy (CRT) paradigm requires pinpointing which candidate cis-regulatory elements (cCREs) are active in human neurons, and which can be targeted with CRISPRa to yield specific and therapeutic levels of target gene upregulation. Here, we combine Massively Parallel Reporter Assays (MPRAs) and a multiplex single cell CRISPRa screen to discover functional human neural enhancers whose CRISPRa targeting yields specific upregulation of NDD risk genes. First, we tested 5,425 candidate neuronal enhancers with MPRA, identifying 2,422 that are active in human neurons. Selected cCREs also displayed specific, autonomous in vivo activity in the developing mouse central nervous system. Next, we applied multiplex single-cell CRISPRa screening with 15,643 gRNAs to test all MPRA-prioritized cCREs and 761 promoters of NDD genes in their endogenous genomic contexts. We identified hundreds of promoter- and enhancer-targeting CRISPRa gRNAs that upregulated 200 of the 337 NDD genes in human neurons, including 91 novel enhancer-gene pairs. Finally, we confirmed that several of the CRISPRa gRNAs identified here demonstrated selective and therapeutically relevant upregulation of SCN2A, CHD8, CTNND2 and TCF4 when delivered virally to patient cell lines, human cerebral organoids, and a humanized mouse model of hTcf4. Our results provide a comprehensive resource of active, target-linked human neural enhancers for NDD genes and corresponding gRNA reagents for CRT development. More broadly, this work advances understanding of neural gene regulation and establishes a generalizable strategy for discovering CRT gRNA candidates across cell types and haploinsufficient disorders.

genomics↗

bioRxiv2025

Dormant viral pathways underlie space-induced neural senescence: a neuroprotective strategy for spaceflight and neurological diseases

Long-duration spaceflight is associated with neurological symptoms in astronauts, yet the underlying molecular mechanisms remain unclear. Using human brain organoids cultured aboard the International Space Station, we analyzed three independent spaceflights to demonstrate that exposure to the space environment triggers Space-Induced Neural Senescence (SINS), characterized by chromatin remodeling, mitochondrial dysfunction, and activation of viral-like transcriptional programs in the absence of infection. Multi-omics analyses identified upregulation of endogenous LINE-1 (L1) retroelements, whose activity was markedly enhanced in organoids lacking MECP2, a known L1 repressor implicated in Rett syndrome. The resulting accumulation of cytoplasmic L1 DNA elicited an IL-6-mediated inflammatory and neurotoxic response, which was reversed by reverse transcriptase inhibitors (RTi) such as lamivudine or stavudine. Parallel preclinical experiments in Mecp2-deficient mice confirmed that RTi treatment restored neuronal morphology, synaptogenesis, function, cognition, and survival. These findings reveal that the space environment reactivates dormant genomic retroelements, providing an unexpected mechanistic insight into astronaut neurobiology and identifying a potential therapeutic strategy for both space-induced and terrestrial neurological conditions. Our pioneering study demonstrates the value of space-enabling research in accelerating drug discovery and disease treatment on Earth.

neuroscience↗

bioRxiv2025

Interregional human assembloids recapitulate fetal brain morphologies and enhance neuronal complexity

Neuronal morphology governs how neurons connect, integrate, and process information, offering critical insights into the functional architecture of the brain. Characterizing the three-dimensional (3D) morphology of individual neurons is key not only for mapping circuit connectivity but also for understanding the cellular diversity that emerges during development. Neural organoids are valuable models of human brain development and disease, yet their morphological complexity remains poorly characterized despite advances in single-cell transcriptomics. Here, we use 3D confocal imaging and manual reconstruction of 735 neurons to analyze forebrain (dorsal and ventral) and thalamic (dorsal and ventral) organoids, as well as forebrain, thalamic, and corticothalamic assembloids. We find that organoids and assembloids exhibit distinct morphologies resembling fetal brain neurons, including immature pyramidal-like, double-bouquet, and bushy-like neurons. Interregional assembloids show greater neuronal morphological complexity than individual organoids, with more extensive dendritic branching, longer projections, and diverse soma shapes. Corticothalamic assembloids further display features of emerging connectivity. We observe dendritic spines with excitatory and inhibitory profiles and varicosities, indicative of maturing synaptic architecture. Together, our work makes an initial effort in describing the diversity of neuronal morphology in human neural organoids and assembloids. It further establishes structural phenotyping as a critical dimension for validating human neural models and underscores their value for modeling morphofunctional disorders.

neuroscience↗

bioRxiv2025

Prenatal Acetaminophen Exposure Does Not Disrupt Human Fetal Brain Development in Cortical Organoid Models

Acetaminophen (APAP) is the most widely used analgesic during pregnancy, yet its effects on prenatal human brain development remain incompletely understood. Epidemiological studies have reported inconsistent associations between prenatal APAP exposure and later neurodevelopmental outcomes, underscoring the need for mechanistic evaluation in human-relevant developmental models. Here, we examined how APAP influences early cortical development using induced pluripotent stem cell-derived cortical organoids (COs) generated from six independent lines. Organoids were exposed to physiologically relevant APAP concentrations (25, 50, and 100 M) for 5 days beginning at day 21 of differentiation, corresponding to late first-trimester cortical development. We assessed organoid growth, apoptosis, differentiation, synaptic maturation, transcriptomic profiles using bulk and single-nucleus RNA sequencing (snRNA-seq), and functional network activity using multielectrode array recordings up to 4 months. APAP exposure did not affect organoid size, cytoarchitecture, or viability. Neuronal and progenitor cell proportions, as well as synaptic puncta density were unchanged. Bulk RNA-seq revealed subtle transcriptional changes only at the highest dose (16 differentially expressed genes at 100 M), enriched for neurodevelopmental pathways. In contrast, snRNA-seq at 3 months revealed no changes in cell type composition or gene expression. Consistent with these findings, electrophysiological measures including firing rate, burst frequency, and network synchrony, were indistinguishable from controls. Together, these results indicate that exposure to therapeutic APAP concentrations during a critical window of early cortical development produces minimal molecular perturbations without detectable consequences. This study provides mechanistic evidence indicating that, in this human organoid model, recommended APAP exposure is not associated with detectable disruptions in pathways implicated in brain development.

neuroscience↗

bioRxiv2025

Integrative Single-Cell Analysis of Autism Spectrum Disorder Animal Models Reveal Convergent Transcriptomic Dysregulation Involved in Excitatory-Inhibitory Imbalance and Glial Disfunction

Autism Spectrum Disorder (ASD) presents profound clinical and etiological heterogeneity, complicating the identification of core pathophysiological mechanisms. Single-cell RNA sequencing (scRNA-seq) offers cellular resolution but integrating findings across diverse studies remains challenging. Here, we constructed a unified single-cell reference framework by integrating scRNA-seq data from 11 distinct genetic and environmental ASD animal models, encompassing over 300.000 cells across various brain regions and developmental stages. Comparative analyses revealed convergent differentially expressed genes (DEGs) across neuronal and glial populations. Cross-model comparisons validated the integration, showing significant concordance between the unified dataset and individual studies, particularly for neuronal populations, and demonstrating how environmental models like valproic acid exposure recapitulate some of the transcriptomic alterations seen in genetic models. Cell communication analyses support widespread excitatory-inhibitory imbalance and with predicted signaling involving ligands like Pdgfa and Reln. Furthermore, we identified significant glial dysfunction, notably downregulation of crucial functional genes in astrocytes and signatures of metabolic dysregulation in mature oligodendrocytes. Cross-referencing with the SFARI database confirmed significant overlap with high-confidence ASD risk genes, with notable dysregulated in specific cell types included Ermn (upregulated in multiple glia), Foxg1 (downregulated in L5/6 NP neurons) and Mef2c (downregulated in MEIS2-like interneurons). Comparison with human scRNA-seq postmortem data revealed conserved dysregulation, highlighting enrichment of presynaptic/postsynaptic translation processes in neurons (implicating CACNAIA, GRIN2B, CAMK2A, ribosomal proteins) along with enrichment for neurodevelopmental disorder pathways in mature oligodendrocytes, involving NRXN and DLGAP gene networks. This integrative study provides unprecedented insight into the convergent cellular and molecular pathologies underlying ASD, establishing a valuable resource for understanding shared mechanisms and identifying new potential therapeutic targets.

neuroscience↗

bioRxiv2024

Graphene-polymer Nanofibers Enable Optically Induced Electrical Maturation in Stem Cell-Derived Cardiomyocytes and Brain Organoids

Human pluripotent stem cell (hPSC)-derived electrically excitable cells provide a unique window into development, but they remain electrically immature partially due to the lack of chronic stimulation. Here, we fabricated electrospun polymer nanofibers containing light-reactive reduced graphene oxide (rGO) as part of a new classes of on-demand, electrically active biomaterials to enhance cell function. Fiber size, stiffness, and electrical conductivity varied with rGO concentration, which impacted hPSC-derived cardiomyocyte and neuron responses; with acute light stimulation, cardiomyocytes exhibited increased, synchronous calcium handling, and neurons showed more calcium peaks with higher frequency. Chronic, repetitive nanofiber light stimulation caused brain organoids to become increasingly electrically active and to activate photoreceptor pathways. This work outlines a tunable method where electrical cell functions can be titrated with rGO fibers and light stimulation, and it suggests that repetitive light stimulation may provide a novel method for retinal differentiation. HIGHLIGHTSO_LIElectrospun graphene-polymer nanofibers electrically respond to light stimulation C_LIO_LILight reactive graphene nanofibers stimulate electrically excitable cells in real-time C_LIO_LIStem cell-derived cardiomyocytes and neurons on nanofibers functionally improve C_LIO_LILight-training of brain organoids induces retinal and excitable neuron maturation C_LI

bioengineering↗

bioRxiv2024

Pathogenic microbiota disrupts the intact structure of cerebral organoids by altering energy metabolism

This study investigated the impact of different bacterial populations on the biomolecular structures of cerebral organoids (COs) at various levels. COs were co-cultured with non-pathogenic (NM) and pathogenic (PM) bacterial populations. PM reduced the number of TUJ1+ neurons and disrupted the intact structure of COs. In addition, PM was found to induce changes in the transcript profile of COs, including a decrease in the activity of the glycolysis pathway and an increase in the pentose phosphate pathway, leading to deterioration in cellular energy metabolism, which is linked to neurodegenerative diseases. Proteomic analysis revealed a unique cluster of proteins in COs. PM exposure upregulated proteins related to neurological diseases, consistent with RNA-seq data. Communication between bacteria and neural cells was demonstrated using 18O-stable isotope labeling (SIL)-based metabolic flux analysis. COs showed higher 18O-enrichment of TCA cycle intermediates when co-cultured with NM and PM, indicating increased oxidative phosphorylation activity upon exposure to bacteria. This study provides a useful platform to monitor metabolic signals and communication between microbiotas and human brain cells. The findings suggest that pathogenic bacteria release metabolites that alter biomolecular structures in brain organoids, potentially contributing to neurodegenerative diseases.

neuroscience↗

bioRxiv2024

Single-Molecule Barcoding Technology for Single-Cell Genomics

Recent advances in barcoding technologies have significantly enhanced the scalability of single-cell genomic experiments. However, large-scale experiments are still rare due to high costs, complex logistics, and laborintensive procedures. To facilitate the routine application of the largest scalability, it is critical to simplify the production and use of barcoding reagents. Here, we introduce AmpliDrop, a technology that initiates the barcoding process using a pool of inexpensive single-copy barcodes and integrates barcode multiplicity generation with tagging of cellular content into a single reaction driven by DNA polymerase during library preparation. The barcoding reactions are compartmentalized using an electronic pipette or a robotic or standalone liquid handling system. These innovations eliminate the need for barcoded beads and complex combinatorial indexing workflows and provide flexibility for a wide range of scales and tube formats, as well as compatibility with automation. We show that AmpliDrop is capable of capturing transcriptomes and chromatin accessibility, and it can also be adapted for user-customized applications, including antibody-based protein detection, bacterial or viral DNA detection, and CRISPR perturbations without dual guide RNA-expression vectors. We validated AmpliDrop by investigating the influence of short-term static culturing on cell composition in human forebrain organoids, revealing metabolic reprogramming in lineage progenitors.

molecular biology↗

bioRxiv2024

Mitochondrial dysfunction heightens the integrated stress response to drive ALS pathogenesis

Vesicle-associated membrane protein-associated protein-B (VAPB) is an ER membrane bound protein. VAPB P56S causes a dominant, familial form of amyotrophic lateral sclerosis (ALS), however, the mechanism through which this mutation causes motor neuron (MN) disease remains unknown. Using inducible wild type (WT) and VAPB P56S expressing iPSC-derived MNs we show that VAPB P56S, but not WT, protein decreased neuronal firing and mitochondrial-ER contact (MERC) with an associated age-dependent decrease in mitochondrial membrane potential (MMP); all typical characteristics of MN-disease. We further show that VAPB P56S expressing iPSC-derived MNs have enhanced age-dependent sensitivity to ER stress. We identified elevated expression of the master regulator of the Integrated Stress Response (ISR) marker ATF4 and decreased protein synthesis in the VAPB P56S iPSC-derived MNs. Chemical inhibition of ISR with the compound, ISRIB, rescued all MN disease phenotype in VAPB P56S MNs. Thus, our results not only support ISR inhibition as a potential therapeutic target for ALS patients, but also provides evidence to pathogenesis.

neuroscience↗

bioRxiv2024

Transcriptional perturbation of LINE-1 elements reveals their cis-regulatory potential

Long interspersed element-1 (LINE-1 or L1) retrotransposons constitute the largest transposable element (TE) family in mammalian genomes and contribute prominently to inter- and intra-individual genetic variation. Although most L1 elements are inactive, some evolutionary younger elements remain intact and genetically competent for transcription and occasionally retrotransposition. Despite being generally more abundant in gene-poor regions, intact or full-length L1s (FL-L1) are also enriched around specific classes of genes and on the eutherian X chromosome. How proximal FL-L1 may affect nearby gene expression remains unclear. In this study, we aim to examine this in a systematic manner using engineered mouse embryonic stem cells (ESCs) where the expression of one representative active L1 subfamily is specifically perturbed. We found that [~]1,024 genes are misregulated following FL-L1 activation and to a lesser extent ([~]81 genes), following their repression. In most cases (68%), misexpressed genes contain an intronic FL-L1 or lie near a FL-L1 (<260 kb). Gene ontology analysis shows that upon L1 activation, up-regulated genes are enriched for neuronal function-related terms, suggesting that some L1 elements may have evolved to control neuronal gene networks. These results illustrate the cis-regulatory impact of FL-L1 elements and suggest a broader role for L1s than originally anticipated.

genomics↗

bioRxiv2024

Accelerated Hematopoietic Stem Cell Aging in Space

Stem cell aging is accelerated by macroenvironmental and microenvironmental stressors, including inflammation. Previously, the NASA Twins study revealed inflammatory cytokine upregulation, chromosomal alterations, and telomere changes suggestive of accelerated aging in low-Earth orbit (LEO). To investigate the effects of spaceflight on human hematopoietic stem and progenitor cell (HSPC) aging, the NASA-supported Integrated Space Stem Cell Orbital Research team performed four independent 30- to 45-day NASA missions with matched flight and ground HSPC nanobioreactors in automated CubeLabs. These experiments revealed loss of HSPC dormancy, reduced self-renewal capacity, mitochondrial DNA amplification, APOBEC3-induced C-to-T mutagenesis, reduced ADAR1p150 expression, and alterations in the expression of repetitive elements. These molecular changes are indicative of accelerated HSPC aging and pre-leukemia stem cell generation in space and may be predictable and preventable.

cancer biology↗

bioRxiv2022

Multimodal monitoring of human cortical organoids implanted in mice using transparent graphene microelectrodes reveal functional connection between organoid and mouse visual cortex

Human cortical organoids, three-dimensional neuronal cell cultures derived from human induced pluripotent stem cells, have recently emerged as promising models of human brain development and dysfunction. Transplantation of human brain organoids into the mouse brain has been shown to be a successful in vivo model providing vascularization for long term chronic experiments. However, chronic functional connectivity and responses evoked by external sensory stimuli has yet to be demonstrated, due to limitations of chronic recording technologies. Here, we develop an experimental paradigm based on transparent graphene microelectrode arrays and two-photon imaging for longitudinal, multimodal monitoring of human organoids transplanted in the mouse cortex. The transparency of graphene microelectrodes permits visual and optical inspection of the transplanted organoid and the surrounding cortex throughout the chronic experiments where local field potentials and multi-unit activity (MUA) are recorded during spontaneous activity and visual stimuli. These experiments reveal that visual stimuli evoke electrophysiological responses in the organoid, matching the responses from the surrounding cortex. Increases in the power of the gamma and MUA bands as well as phase locking of MUA events to slow oscillations evoked by visual stimuli suggest functional connectivity established between the human and mouse tissue. Optical imaging through the transparent microelectrodes shows vascularization of the organoids. Postmortem histological analysis exhibits morphological integration and synaptic connectivity with surrounding mouse cortex as well as migration of organoid cells into the surrounding cortex. This novel combination of stem cell and neural recording technologies could serve as a unique platform for comprehensive evaluation of organoids as models of brain development and dysfunction and as personalized neural prosthetics to restore lost, degenerated, or damaged brain regions.

neuroscience↗

bioRxiv2021

EXPRESSION OF A SECRETABLE, CELL-PENETRATING CDKL5 PROTEIN ENHANCES THE EFFICACY OF AAV VECTOR-MEDIATED GENE THERAPY FOR CDKL5 DEFICIENCY DISORDER.

No therapy is currently available for CDKL5 (cyclin-dependent kinase-like 5) deficiency disorder (CDD), a severe neurodevelopmental disorder caused by mutations in the CDKL5 gene. Although delivery of a wild-type copy of the mutated gene to cells represents the most curative approach for a monogenic disease, proof-of-concept studies highlight significant efficacy caveats for brain gene therapy. Herein, we used a secretable TATk-CDKL5 protein to enhance the efficiency of a gene therapy for CDD. We found that, although AAVPHP.B_Igk-TATk-CDKL5 and AAVPHP.B_CDKL5 vectors had similar brain infection efficiency, the AAVPHP.B_Igk-TATk-CDKL5 vector led to a higher CDKL5 protein replacement due to secretion and transduction of the TATk-CDKL5 protein into the neighboring cells. Importantly, Cdkl5 KO mice treated with the AAVPHP.B_Igk-TATk-CDKL5 vector showed a behavioral and neuroanatomical improvement in comparison with vehicle-treated Cdkl5 KO mice or Cdkl5 KO mice treated with the AAVPHP.B_CDKL5 vector, indicating that a gene therapy based on a secretable recombinant TATk-CDKL5 protein is more effective at compensating Cdkl5-null brain defects than gene therapy based on the expression of the native CDKL5.

neuroscience↗

bioRxiv2021

All-optical electrophysiology in hiPSC-derived neurons with synthetic voltage sensors

Voltage imaging and "all-optical electrophysiology" in human induced pluripotent stem cell (hiPSC)-derived neurons have opened unprecedented opportunities for high-throughput phenotyping of activity in neurons possessing unique genetic backgrounds of individual patients. While prior all-optical electrophysiology studies relied on genetically encoded voltage indicators, viral transduction of human neurons with large or multiple expression vectors can impact cell function and often lead to massive cell death. Here, we demonstrate an alternative protocol using a synthetic voltage sensor and genetically encoded optogenetic actuator that generate robust and reproducible results. We demonstrate the functionality of this method by measuring spontaneous and evoked activity in three independent hiPSC-derived neuronal cell lines with distinct genetic backgrounds.

neuroscience↗

bioRxiv2020

Understanding the Human Brain using Brain Organoids and a Structure-Function Theory

A basic neurobiology-clinical trial paradigm motivates our use of constrained mathematical models and analysis of personalized human-derived brain organoids toward predicting clinical outcomes and safely developing new therapeutics. Physical constraints imposed on the brain can guide the analyses an interpretation of experimental data and the construction of mathematical models that attempt to make sense of how the brain works and how cognitive functions emerge. Development of these mathematical models for human-derived brain organoids offer an opportunity for testing new hypotheses about the human brain. When it comes to testing ideas about the brain that require a careful balance between experimental accessibility, manipulation, and complexity, in order to connect neurobiological details with higher level cognitive properties and clinical considerations, we argue that fundamental structure-function constraints applied to models of brain organoids offer a path forward. Moreover, we show these constraints appear in canonical and novel math models of neural activity and learning, and we make the case that constraint-based modeling and use of representations can bridge to machine learning for powerful mutual benefit.

neuroscience↗

bioRxiv2020

Cortical Organoids Model Early Brain Development Disrupted by 16p11.2 Copy Number Variants in Autism

Reciprocal deletion and duplication of 16p11.2 region is the most common copy number variation (CNV) associated with Autism Spectrum Disorders. We generated cortical organoids from skin fibroblasts of patients with 16p11.2 CNV to investigate impacted neurodevelopmental processes. We show that organoid size recapitulates macrocephaly and microcephaly phenotypes observed in the patients with 16p11.2 deletions and duplications. The CNV has mirror-opposite effect on neuronal maturation, proliferation, and synapse number, in concordance with its effect on brain growth in humans. We demonstrate that 16p11.2 CNV alters the ratio of neurons to neural progenitors in organoids during early neurogenesis, with excess of neurons and depletion of neural progenitors observed in deletions, and mirror phenotypes in duplications. Transcriptomic and proteomic profiling revealed multiple dysregulated pathways, including defects in neuron migration. Inhibition of activity of the small GTPase RhoA rescued migration deficits. This study provides insights into potential neurobiological mechanisms behind the 16p11.2 CNV during neocortical development.

neuroscience↗