Date of Award
Doctor of Philosophy (PhD)
Cell & Molecular Biology
Meera V. Sundaram
Tubular epithelial cells are one of the most abundant cell types in multicellular organisms. Tubular cells transport gases and liquids, and funnel harmful excretory waste from our bodies. It is clear that Receptor Tyrosine Kinase (RTK) signaling is essential for the formation of many tubular organs such as our kidneys and blood vessels. However, which steps in tube development require RTK signaling is less well understood. The C.elegans excretory system is a primitive renal system with just three essential cells (duct, pore, and canal cells), providing a simple yet dynamic system to study tube specification and morphogenesis. In the C.elegans excretory system, we demonstrated that the EGF-Ras-Erk signaling pathway specified the excretory duct tube versus the pore tube fate. In addition, EGF-Ras-Erk signaling influenced the positions that the duct and pore cells adopted within the tubular network. And finally, after position and fate determination, EGF-Ras-Erk signaling had a continued role in maintaining organ architecture of the duct tube. Goals for future research will be to determine how EGF-Ras-ERK signaling controls these genetically distinct steps during tube development.
In a separate project, I studied the Nkx5 homeodomain transcription factor, MLS-2, which was identified in a mutagenesis screen by a former graduate student in the lab. I discovered a role for MLS-2 in promoting proper cell shape of the duct and pore. mls-2 cooperated with the EGF-Ras-Erk pathway to turn on lin-48/Ovo during duct morphogenesis. I speculate that MLS-2 and other Nkx5 family members have conserved functions in promoting shape acquisition in cells that adopt complex morphologies similar to the duct and pore.
Abdus-Saboor, Ishmail, "The Egf-Ras-Erk Pathway and the Nkx-5/hmx Homeodomain Protein Mls-2 Promote Tube Development in the C.elegans Excretory System" (2012). Publicly Accessible Penn Dissertations. 484.