Biology subjects

Kershner, A. M.

Publications and source records attributed to Kershner, A. M..

2 recordsLinked to original sources

bioRxiv2021

A sensitized genetic screen to identify regulators of C. elegans germline stem cells

Germline stem cells (GSCs) in Caenorhabditis elegans are maintained by GLP-1/Notch signaling from the niche and by a downstream RNA regulatory network. Loss of the GLP-1 receptor causes GSCs to precociously undergo meiotic differentiation, the "Glp" phenotype, due to a failure to self-renew. lst-1 and sygl-1 are functionally redundant direct targets of GLP-1 signaling whose gene products work with PUF RNA binding proteins to promote GSC self-renewal. Whereas single loss-of-function mutants are fertile, lst-1 sygl-1 double mutants are sterile and Glp. We set out to identify genes that function redundantly with either lst-1 or sygl-1 to maintain GSCs. To this end, we conducted forward genetic screens for Glp mutants in genetic backgrounds lacking functional copies of either lst-1 or sygl-1. The screens generated nine glp-1 alleles, two lst-1 alleles, and one allele of pole-1, which encodes the catalytic subunit of DNA polymerase {varepsilon}. Three glp-1 alleles reside in Ankyrin (ANK) repeats not previously mutated. pole-1 single mutants have a low penetrance Glp that is enhanced by loss of either lst-1 or sygl-1. Thus, the screen uncovered one locus that interacts genetically with both lst-1 and sygl-1 and generated useful mutations for further studies of GSC regulation.

genetics↗

bioRxiv2019

LST-1 acts in trans with a conserved RNA-binding protein to maintain stem cells

Stem cell self-renewal is essential to development and tissue repair. The C. elegans LST-1 protein is a pivotal regulator of self-renewal and oncogenic when misexpessed. Here we define regions within the LST-1 protein that provide molecular insights into both its function and regulation. LST-1 self-renewal activity resides within a predicted disordered region that harbors two KXXL motifs. These KXXL motifs mediate LST-1 binding to FBF, a broadly conserved Pumilio/PUF RNA-binding protein that represses differentiation. Point mutations of the KXXL motifs abrogate LST-1 self-renewal activity. Therefore, FBF binding is essential to LST-1 function. A second distinct region regulates LST-1 spatial expression and primarily affects LST-1 protein turnover. Upon loss of this regulatory region, LST-1 protein distribution expands and drives formation of a larger than normal GSC pool. Thus, LST-1 promotes self-renewal as a key FBF partner, and its spatial regulation helps determine size of the GSC pool.\n\nIMPACT STATEMENTA key stem cell regulator partners with a broadly conserved PUF RNA-binding protein to drive self-renewal and maintain a stem cell pool.

developmental biology↗