Biosciences Research Seminar - Sending and Receiving the Hedgehog Signal

Part of the Biosciences lunchtime research seminar series

A Biosciences seminar
Date5 November 2020
Time12:30 to 13:30
PlaceVia TEAMS

Speaker: Dr Stacey Ogden, Cell & Molecular Biology, St. Jude Children's Research Hospital, Memphis. Host: Dr Steffen Scholpp. Seminar held via Teams.


Abstract

The Sonic Hedgehog (SHH) pathway is an essential driver of tissue morphogenesis and homeostasis that, when corrupted, can lead to developmental syndromes and cancer. I will discuss two projects focused on defining molecular mechanisms promoting SHH signaling activity. The first aims to understand how SHH ligands are deployed from signal producing cells and trafficked to distantly localized target cells through specialized filopodia called cytonemes. We discovered that SHH localizes to cytonemes in complex with the SHH deployment protein Dispatched and the adhesion molecule BOC or CDO. The SHH complex is transported to cytoneme tips by the actin motor protein Myosin 10, which when mutated, attenuates cytoneme-based SHH delivery and disrupts tissue patterning. The second project examines how SHH-regulated lipid metabolism links signal initiation with fitness of the primary cilium, a sensory organelle that orchestrates the SHH response in ligand-receiving cells. We mapped a novel signal relay driven by SHH-stimulated arachidonic acid production that links active SHH signaling with maintenance of primary cilia length through the prostaglandin E2 (PGE2) pathway. Arachidonic acid serves as a lynchpin connecting SHH and PGE2 signals by directly binding the SHH signal transducing protein Smoothened to promote its ciliary entry, and by providing a localized source for PGE2 production to promote ciliary elongation through EP4 receptor activation.

Attachments
Seminar_Series_Poster_05112020.pdf (259K)

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