Sonic Hedgehog Dependent Neuron-Astrocyte Crosstalk During Cortical Circuit Assembly

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Principal Investigator: COREY C HARWELL
Organization: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
Fiscal Year: 2024
Award: $376,474
Funding agency: National Institute of Neurological Disorders and Stroke

Project Summary
Neuronal-glial relationships play a critical role in the regulation of synapse formation and neuronal
specification. The cellular and molecular mechanisms by which neurons and astrocytes communicate and
coordinate are not well understood. The experiments in this proposal will uncover the molecular and cellular
mechanisms by which neuron derived SHH protein can coordinate the cell behaviors of cortical astrocytes to
facilitate the formation and function of neural circuits in the brain. In our studies we take advantage of the large
complement of mouse genetic tools that allows us to specifically manipulate Shh signaling in astrocytes. Using
cutting edge light and electron microscopy approaches we will define how specific interactions between
astrocytes and neurons are dependent on Shh signaling and assess how astrocytes influence the development
of functional circuits. Collectively these aims will provide a framework for understanding the delivery, reception
and cellular response to SHH in the developing cortex.

Terms: <ASD><Ablation><Adhesion Molecule><Assay><Astrocytes><Astrocytus><Astroglia><Autism><Autistic Disorder><Autoregulation><Behavior><Bioassay><Biological Assay><Brain><Brain Nervous System><Brothers><Cell Adhesion Molecule Gene><Cell Adhesion Molecules><Cell Communication and Signaling><Cell Function><Cell Physiology><Cell Process><Cell Signaling><Cellular Function><Cellular Physiology><Cellular Process><Cerebral cortex><Chemical Synapse><Communication><Complement><Complement Proteins><Complex><Data><Development><Early Infantile Autism><Electrical Synapse><Electron Microscopy><Electrophysiology><Electrophysiology (science)><Encephalon><GLI Family Gene><GLI Family Protein><GLI Protein><GLI gene><GLI1><GLI1 Gene><GLI1 Protein><Gene Expression><Gene Transcription><Genes><Genetic><Genetic Transcription><Glia><Glial Cells><Glioma Associated Oncogene Homolog 1 Protein><Glioma Associated Oncogene Homolog Protein><Glioma-Associated Oncogene Homolog><Histology><Homeostasis><Human><Infantile Autism><Intellectual disability><Intellectual functioning disability><Intellectual limitation><Intracellular Communication and Signaling><Ions><Kanner's Syndrome><Kolliker's reticulum><Maintenance><Mediating><Modern Man><Molecular><Nature><Nerve Cells><Nerve Unit><Nervous System><Neural Cell><Neurocyte><Neurodevelopmental Disorder><Neuroglia><Neuroglial Cells><Neurologic Body System><Neurologic Organ System><Neurological Development Disorder><Neurons><Neurophysiology - biologic function><Neurophysiology / Electrophysiology><Non-neuronal cell><Nonneuronal cell><Pathway interactions><Performance><Physiological Homeostasis><Play><Process><Proteins><Publishing><RNA Expression><Receptor Protein><Regulation><Role><SHH><SHH gene><Signal Pathway><Signal Transduction><Signal Transduction Systems><Signaling><Single-Nucleus Sequencing><Sonic Hedgehog><Specific qualifier value><Specificity><Specified><Subcellular Process><Synapses><Synaptic><Testing><Therapeutic Intervention><Transcription><Work><astrocytic glia><autism spectral disorder><autism spectrum disorder><autistic spectrum disorder><biological signal transduction><cell adhesion protein><cell behavior><cell type><cellular behavior><complementation><cytokine><developmental><electrophysiological><experiment><experimental research><experimental study><experiments><glioma associated oncogene 1><glioma associated oncogene family zinc finger 1><insight><intellectual and developmental disability><intervention therapy><light microscopy><limited intellectual functioning><loss of function><mouse genetics><mutant><nerve cement><neural circuit><neural circuitry><neural function><neurocircuitry><neurodevelopmental disease><neuronal><neurotransmitter reuptake><pathway><programs><receptor><response><sNuc-Seq><single nucleus RNA-sequencing><single nucleus seq><single-nucleus RNA-seq><snRNA sequencing><snRNA-seq><social role><synapse><synapse formation><synapse function><synaptic circuit><synaptic circuitry><synaptic function><synaptogenesis><therapeutic agent development><therapeutic development><tool>