The role of Hh signaling in mouse retinal bipolar cell subtype development

• Main Author: Wu, Di
• Other Authors: Chow, Robert Lewis
• Format: Others
• Language: English; en
• Published: 2017
• Subjects: Retina; Bipolar cell; Sonic Hedgehog; Smoothened; Signaling; Development
• Online Access: https://dspace.library.uvic.ca//handle/1828/8409

In the vertebrate retina, bipolar interneurons consist of at least 13 distinct subtypes, which are classified based on their morphology, behavior and gene expression. The mechanisms underlying the formation of these subtypes is poorly understood. Our previous unpublished work has implicated Sonic Hedgehog (Shh) in the formation of cone and rod bipolar cell subtypes. In this thesis, I characterized the relationship between Hh signaling and bipolar subtype cell development in greater detail. Using an in vivo plasmid-based reporter approach, I show that Hh signaling is active in both retinal progenitor cells (RPCs) and bipolar cells of the postnatal retina. Next, to address function, I used a conditional gene targeting approach to show that activation of Smoothened (Smo), a downstream Hh signaling component, is both necessary and sufficient in postnatal RPCs to promote the formation of cone but not rod bipolar cells. In contrast, activation of Smo in postmitotic bipolar cells that are greater than 24 hours old from cell birth, does not affect bipolar subtype formation. Together, these results suggest that Hh signaling functions in postnatal RPCs (and potentially in early bipolar cell precursors) to promote cone bipolar cell formation. === Graduate === 2018-06-12