Neuronal form drives function. Morphology is a core determinant of neuronal identity—regulating connectivity, physiology, and behavior. While large-scale features of neuronal morphology are often stable, fine-scale adjustments contribute to neuronal plasticity and function throughout life. It is essential to characterize molecular and cellular mechanisms contributing to the delicate balance of stability and plasticity that underlie many of the remarkable attributes of the nervous system. We investigate how neurons establish and maintain their distinctive morphologies, as well as how they can be remodeled in response to developmental or environmental cues. We are currently investigating two related questions.

1. How are neuronal microtubule dynamics regulated in response to extracellular cues? At a cellular level, the competing properties of morphological stability and plasticity are conferred by the cytoskeleton. In particular, the microtubule cytoskeleton not only bestows neuronal processes with the structural stability essential for long-term connectivity, but also enables the plasticity necessary for outgrowth, circuit remodeling, and normal functional synaptic plasticity. Given that microtubule dysfunction is implicated in diverse motorneuron and neurodegenerative disorders, understanding molecular regulation of the microtubule cytoskeleton is a necessary foundation for understanding disease pathogenesis and developing new therapeutic approaches.

2. How is signaling pathway activity controlled at synapses? By definition, neurotransmitter is released from the presynaptic compartment and received by neurotransmitter receptors on the postsynaptic side. However, extracellular signaling pathway activity is not circumscribed in this way and may occur at short or long range at multiple subcellular positions. Hence, neurons are likely to possess fine-regulatory mechanisms controlling the release of, and response to, extracellular cues. We are using the Drosophila NMJ as a model synapse to understand the molecular mechanisms establishing directionality of BMP pathway activity.

Dr. Broihier, a Cleveland native, received her Ph.D. from M.I.T. in 1998 and was a postdoctoral fellow at Washington University in St. Louis.

1. Nechipurenko, IV, Broihier HT. (2012)
   FoxO limits microtubule stability and is itself negatively regulated by microtubule disruption. Journal of Cell Biology. 2012 Feb; 196(3):345-362.
   
2. James RE, Broihier HT. (2011)
   Crimpy inhibits the BMP homolog Gbb in motoneurons to enable proper growth control at the Drosophila neuromuscular junction. Development. 2011 July; 138(15):3273-3286.
   
3. Miller CM, Liu N, Page-McCaw A, Broihier HT. (2011)
   Drosophila Mmp2 regulates the matrix molecule faulty attraction (Frac) to promote motor axon targeting in Drosophila. Journal of Neuroscience. 2011 April; 31(14):5335-5347.
   
4. Weng YL, Liu N, DiAntonio, A, Broihier HT. (2011)
   The cytoplasmic adaptor protein Caskin mediates Lar signal transduction during Drosophila motor axon guidance. Journal of Neuroscience. 2011 March; 23(31):4421-4133.