Event Information:
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Thu09May201912:00 PMAula M6, Edifici Margalef, Biology Faculty
NCS 2019 "The Importance of Signaling Pathway Downregulation for Central Nervous System Development and Homeostasis"
Sergi Simó, PhD | University California Davis
Abstract
lopment, neurons migrate, mature, and integrate into the existing network following an intricate set of cues. Similarly, in the adult brain, homeostasis is achieved by responding to cues that regulate a myriad of processes, including adult neurogenesis. Cells respond to all these cues by triggering signaling pathways that, once the information is transduced, must be downregulated. Inappropriate regulation of signaling pathways cause neurons to mismigrate, lose responsiveness to new signals, and/or sustain the original signaling response, causing harm or death to the cell. The E3 Cullin-5 RING ligase (CRL5) is a crucial regulator of neuron migration and cell position in the retina, cortex, and cerebellum, by downregulating the Reelin/Dab1 signaling pathway. However, the role of CRL5 in the developing and adult hippocampus has remained elusive. Our work shows that CRL5 regulates lamination of hippocampal pyramidal neurons and dentate gyrus, mossy fiber innervation, and adult neurogenesis. We demonstrate that CRL5 participates in these events by regulating on at least two different signaling pathways. CRL5 downregulates the Semaphorin-3F signaling pathway to promote mossy fiber axon pruning, establishing proper mossy fiber innervation and opposes the Reelin/Dab1 signaling to control proper adult neurogenesis. Overall, we identified CRL5 as a novel regulator of hippocampal morphogenesis and homeostasis and propose CRL5-regulated signaling pathways involved in these events.