Project Summary/Abstract
Primary cilia are sensory organelles of a few microns that are present on most vertebrate cells. They convert
surrounding cues into intracellular signals that are critical for cellular functions. The cilium concentrates key
regulators of the Sonic Hedgehog pathway and a wide range of versatile classes of molecules, including G
protein-coupled receptors and second messengers. Despite the clear importance of cilia during embryonic
development and the homeostasis of many tissues and organs, the mechanisms that govern the regulation of
cilia themselves remain unclear. Primary cilia dysfunction causes a variety of developmental syndromes with
neurological defects and cognitive impairment. Even though most neurons have a primary cilium, it is still
unknown how this organelle modulates neuron morphology and connectivity. The long-term goals of my
research group are to i) discover novel mechanisms and processes that govern cilium biogenesis, ii) define the
fundamentals of how and why the cilium dynamically remodels itself, and iii) uncover the underexplored roles of
neuronal cilia in the brain. In the absence of such knowledge, identifying potential tractable modifiers of cilia
regulation will remain difficult, particularly in the brain. We employ an interdisciplinary approach using unbiased
screening strategies, mouse models, cutting-edge microscopy, and cell and molecular biology. The
advancements made over the last five years have been critical in identifying novel molecular foundations of
primary cilia dynamics and ciliary composition in neurons. We will keep building on these first steps to help
advance therapeutic strategies targeting perturbed ciliary pathways.