2021 Theses Doctoral
Investigations into a bHLH code for Caenorhabditis elegans somatic gonad regulatory cell fate and function
The Caenorhabditis elegans somatic gonad is patterned by the activity of regulatory cell types, which govern its morphology, serve as the germline niche, and pattern its connection to the outside. All regulatory cell types are specified by activity of the basic helix-loop-helix gene hlh-2/E/Daughterless, and differences in how functions are assigned between the regulatory cells in males and hermaphrodites lead directly to their sexually-dimorphic gonads. Here, I present evidence that a code of bHLH genes function together with hlh-2 to promote the specification and function of each regulatory cell type except for the hermaphrodite anchor cell, which is specified by HLH-2 activity alone.
Each regulatory cell type expresses an overlapping but distinct set of bHLH genes, which we find are required for its specification and associated functions. Notably, ectopic expression of regulatory cell bHLH complements are sufficient to transform cells with anchor cell potential into the expected regulatory cell, albeit transiently, suggesting that they are master regulators of regulatory cell fate. As all nematode species pattern their gonads through cognate regulatory cells and bHLH genes are highly conserved, we hypothesized that a similar bHLH code might function in specifying the regulatory cells of other species. In some nematode species the anchor cell, which remains stationary in C. elegans, is able to migrate.
In C. elegans, the bHLH gene hlh-12 is necessary for proper migration of hermaphrodite distal tip cells and male linker cell, the two migrating regulatory cell types; addition of hlh-12 to the C. elegans anchor cell causes it to become displaced in a manner dependent on the endogenous hermaphrodite distal tip cell and male linker cell machinery, suggesting that the anchor cell gains the ability to migrate with the addition of hlh-12. We thus hypothesized that ectopic expression of an hlh-12 ortholog in these species might have led them to evolve migrating anchor cells. However, phylogenetic analysis of the bHLH genes of several other species, including the ones with migratory anchor cells, suggests that hlh-12 may be novel to the Caenorhabditis genus and does not have orthologs in the species with migrating anchor cells, raising the possibility that either these species use another bHLH gene for migration or that their regulatory cells are specified in a bHLH-independent manner.
- bHLH ortholog table.xlsx application/vnd.openxmlformats-officedocument.spreadsheetml.sheet 52.5 KB Download File
- Figure S3 10 species tree.pdf application/pdf 10.9 KB Download File
- Hana Littleford Figure S4-4.pdf application/pdf 32 KB Download File
- Hana Littleford Table S4-1.xlsx application/vnd.openxmlformats-officedocument.spreadsheetml.sheet 107 KB Download File
- Figure S5 caenorhabditis diploscapter tree.pdf application/pdf 11.9 KB Download File
- Littleford_columbia_0054D_16381.pdf application/pdf 5.22 MB Download File
More About This Work
- Academic Units
- Biological Sciences
- Thesis Advisors
- Greenwald, Iva
- Ph.D., Columbia University
- Published Here
- February 23, 2021