Sarah Knox, PhD

Core

My goal is to investigate how neuronal-epithelial interactions control organogenesis and regeneration. My work primarily utilizes the mouse embryonic submandibular gland ex vivo model system to examine the role of the parasympathetic ganglion in epithelial branching morphogenesis and regeneration.

The submandibular gland has an autonomic ganglion located in and around the glandular epithelium from the earliest stages of development, and remains with the gland after dissection for ex vivo organ culture. This makes the salivary gland an exceptional model for understanding the influence of the peripheral nervous system on organogenesis and repair processes. During my post-doctorate I discovered that the parasympathetic ganglion plays a critical role in submandibular gland morphogenesis by maintaining keratin 5+ epithelial stem/progenitor cells through an acetylcholine /muscarinic/epidermal growth factor receptor pathway. In addition, I found this pathway maintains progenitor cells in the developing prostate and the adult submandibular gland. More recently I have also established that the neurotrophic factor neurturin secreted by the submandibular gland epithelium is required for parasympathetic ganglion function and survival, and increases organ regeneration after injury. Current projects examine 1) the regulation of stem cell factors by the nervous system during development and regeneration; 2) understanding how stem cells and the nerves are influenced by therapeutic radiation and disease; and 3) how neurotransmitters regulate epithelial architecture and stem cell movement during organogenesis. To investigate these processes we use a combination of genetic and biochemical approaches with the aim of correlating our findings with human tissue.