Sonic hedgehog is required for the formation of auditory ganglion in the mouse inner ear
Wednesday, September 12, 2018 — Poster Session I
- LS Wong
- DK Wu
Hearing loss affects over 300 million people worldwide and yet restorative treatment is minimal as we lack understanding on how our hearing organ, cochlea of the inner ear, is normally formed and wired. The auditory system requires proper connections between sensory hair cells in the cochlea and auditory processing centers in the brain via neurons of the spiral ganglion (SG). Our lab has found that sonic hedgehog (Shh), which encodes a secreted signaling molecule, expresses in the developing SG that is crucial for regulating the timing of hair cell differentiation within the cochlea. However, the significance of this dynamic Shh expression pattern on SG formation is not known. To address this question, a combination of in situ hybridization, lineage tracing, and cell cycle labeling techniques were used to decipher the spatiotemporal origin of the Shh-positive cells in the SG. My research show that Shh is turned on only in nascent post-mitotic SGNs and is down-regulated within two days as the neurons mature. This transient expression of Shh is important as neuroblasts adjacent to the Shh-positive neurons express the Shh receptor, Patched 1 (Ptc1), suggesting that they are responding to Shh signaling. Without Shh, Ptc1 expression is downregulated and the size of SG is much reduced. These results indicate for the first time that an auto-regulatory loop of Shh signaling controls the developmental timing of SG. Understanding how Shh signaling is being regulated in the developing SG will provide insights into how to restore damaged SG.
Category: Developmental Biology