Heather Broihier, PhD

Professor
Department of Neurosciences
School of Medicine
Director
Neurosciences PhD Program
School of Medicine
Deputy Director
Medical Scientist Training Program
School of Medicine

Teaching Information

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Research Information

Research Interests

Circuit formation and remodeling in development and disease

We are developmental neurobiologists studying how circuits form during development, and how circuit disruption causes disease. We focus on neuron-intrinsic mechanisms of synapse formation, and also on how interactions between neurons and glia regulate circuit development and function. We primarily study these questions in Drosophila since the majority of proteins are evolutionarily conserved. Moreover, the short generation time and vast genetic toolkit in this system make it an unsurpassed in vivo model to define conserved principles of neurodevelopment.

Synapse Organization in Health and Disease
Synapse size and strength is tightly controlled and requires tight coordination between pre- and post-synaptic neurons. We study several molecules necessary for synaptogenesis including a2d proteins, which are best known as voltage-gated Ca2+ subunits, and also play conserved roles as synapse organizers. We employed CRISPR-based genome engineering to generate a large panel of new a2d alleles linked to autism-spectrum disorders (ASDs) and intellectual disability and are characterizing their synaptic phenotypes.

We have long been fascinated by growth factor signaling at synapses. We are interested in a protein called Crimpy, a transmembrane protein with TGFb and IGF binding domains, and have characterized its roles in activity-dependent TGFb signaling
at the NMJ. We now focus on investigating Crimpy’s functions regulating IGF signaling in the adult brain, and in collaboration with the Tabuchi lab, its contribution to circadian behavior. Excitingly, we now also study Crimpy’s mouse ortholog, called Crim1, in mammalian motorneuron development, together with the Philippidou lab.

Critical Period Plasticity
Nervous system development is marked by periods of plasticity, called critical periods, in which circuits display remarkable sensitivity to sensory stimuli. Critical period plasticity is distinct from other forms of plasticity because (1) circuits are uniquely capable of structural and/or functional remodeling during these periods, (2) they occur shortly after circuit formation, and (3) critical period remodeling leads to long-term changes in circuit function.

Our current interest in critical period plasticity stems from previous work in our lab that uncovered roles for innate immune signaling in neuron-glia interactions. Specifically, Toll receptor signaling controls Draper/MEGF10/Jedi-1 receptor expression to regulate
glial engulfment of dying neurons during development. We extended this work and found that Draper is also required for synapse pruning in the olfactory circuit during early adulthood. The first two days of adult life represent a well-defined critical period
in this circuit, and ongoing work in the lab seeks to understand how innate immune interactions between neurons and glia control critical period plasticity in this circuit.

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Publications

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Selected Publications

  1. Darren A Jindal, Hans C Leier, Gabriela Salazar, Alexander J Foden, Elizabeth A Seitz, Abigail J Wilkov, Jaeda C Coutinho-Budd, Heather T Broihier. (2023) Early Draper-mediated glial refinement of neuropil architecture and synapse number in the Drosophila antennal lobe. Frontiers in Cellular Neuroscience 10.3389/fncel.2023.1166199

  2. Kelsey A Herrmann, Yizhou Liu, Arnau Llobet-Rosell, Colleen N McLaughlin, Lukas J Neukomm, Jaeda C Coutinho-Budd, Heather T Broihier(2022) Divergent signaling requirements of dSARM in injury-induced degeneration and developmental glial phagocytosis. PLOS Genetics 10.1371/journal.pgen.1010257

  3. Kendall M Hoover, Scott J Gratz, Nova Qi, Kelsey A Herrmann, Yizhou Liu, Jahci J Perry-Richardson, Pamela J Vanderzalm, Kate M O'Connor-Giles, Heather T Broihier. (2019) The calcium channel subunit α2δ-3 organizes synapses via an activity-dependent and autocrine BMP signaling pathway. Nature Communications 10.1038/s41467-019-13165-7

  4. Colleen N. McLaughlin, Jahci J. Perry-Richardson, Jaeda C. Coutinho-Budd, Heather T. Broihier. (2019) Dying Neurons Utilize Innate Immune Signaling to Prime Glia for Phagocytosis during Development. Developmental Cell 48(4):506-22. Cover article.