Defining Molecular Principles of Sensory Neurons in the GCD Olfactory System
Bloom, Maria Lissitsyna
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CitationBloom, Maria Lissitsyna. 2020. Defining Molecular Principles of Sensory Neurons in the GCD Olfactory System. Doctoral dissertation, Harvard University, Graduate School of Arts & Sciences.
AbstractAnimals depend on their sense of smell to survive and reproduce. In mammals, parallel olfactory circuits are specialized to draw information from ethologically relevant chemical cues in the environment. Olfactory sensory neurons (OSNs) in the nose define the inputs to these circuits. While numerous studies have characterized OSNs of the canonical olfactory system, molecular mechanisms that underlie the existence and function of sensory neurons of the specialized guanylate-cyclase D (GCD) expressing ”necklace” olfactory subsystem remain unaccounted for.
Canonical OSNs detect odors through expression of a single receptor from a large family of G-protein coupled olfactory receptor genes. Olfactory capability is maintained by ongoing OSN turnover with distinct molecular and spatial differentiation signatures. Sensory neurons of the GCD system are clustered within caudal recesses of olfactory epithelium populated by canonical neurons and detect a diverse range of odors. However, they do not express typical markers or known olfactory receptors and have not been examined for postnatal replacement.
We used nucleoside birthdating and expression analysis to examine the mechanisms of population maintenance and odorant detection by GCD sensory neurons. We find that new GCD neurons are born throughout adulthood and show that GCD OSN differentiation is characterized by a novel maturity marker with neuromodulatory potential and by an atypical migratory pattern. In a parallel study, we demonstrate that members of the MS4A gene family act as chemoreceptors in GCD sensory neurons. We characterize ligand response properties of olfactory MS4A receptors using calcium imaging and find that MS4As are expressed in a multiple-receptor-per-GCD-neuron pattern. Thus, sensory neurons of the GCD system share broad features of population maintenance with canonical OSNs but employ distinct differentiation and odorant receptor expression programs that likely shape functional specialization of the circuit.
Citable link to this pagehttps://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37365118
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