ACHEMS 2025
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SPLTRAK Abstract Submission
Poster #332
Navigating the Where and What? δ-Protocadherins are Critical for Vomeronasal Neuron Targeting in the Accessory Olfactory Bulb
Nikki Dolphin & Paolo E. Forni
Department of Biological Sciences, Center for Neuroscience Research, The RNA Institute, Albany, NY,

The assembly of functional neural circuits is a highly coordinated process that requires precise control over axon guidance and selective cell-cell interactions. Our understanding of how neurons identify, select, and connect to suitable synaptic partners remains incomplete. Altered neuronal connectivity has been linked to significant neurological disorders, including autism and schizophrenia. Our research aims to unravel the mechanisms involved in neuronal guidance and cell-cell interactions by studying the accessory olfactory system (AOS) in rodents, which includes the vomeronasal organ (VNO) and the accessory olfactory bulb (AOB). Utilizing mouse genetics and single-cell transcriptomics, we examined the role of non-clustered/δ-protocadherins in neuronal spatial segregation and connectivity. Our findings indicate distinct combinatorial expression patterns of non-clustered protocadherins in vomeronasal sensory neurons (VSNs) that express different vomeronasal receptors and their target cells. Furthermore, our data highlight the crucial role of the δ-protocadherin repertoire in axon guidance and connectivity within the AOB. Specifically, observations regarding Pcdh7 and Pcdh9 reveal that they compromise regional axon segregation and affect the number and size of glomeruli formed by VSNs with their targeted mitral cells (MCs). Additionally, observations from Nrp2 knockout (KO) mice suggest that Semaphorin III-mediated axon segregation in the AOB may have epistatic interactions with δ-protocadherins. Overall, our research provides important insights into how changes in protocadherin expression or function can shape the connectivity of chemosensory neurons to the brain.