PhD in Molecular Cell Biology and Neuroscience
Graduate School of Biomedical Sciences, School of Osteopathic Medicine
Virtua College of Medicine and Life Sciences of Rowan University
Eric Moss, PhD
Committee Member 1
Ronald Ellis, PhD
Caenorhabditis elegans, Ikaros Transcription Factor, Transcription Factors, Gene Expression Regulation
Cell Biology | Genetic Processes | Laboratory and Basic Science Research | Medical Cell Biology | Medicine and Health Sciences | Molecular Biology | Molecular Genetics
In Caenorhabditis elegans, the heterochronic pathway is comprised of a hierarchy of genes that control the proper timing of developmental events. hbl-1 (Hunchback Like-1) encodes an Ikaros family zinc-finger transcription factor that promotes the L2 stage cell fate events of the hypodermis. The downregulation ofhbl-1 is a crucial step for the transition from the L2 to the L3 stage. There are two known processes through which negative regulation of hbl-1 occurs: suppression of hbl-1 expression by 3 let-7 miRNAs through the hbl-1 3’UTR and inhibition of HBL-1 activity by LIN-46. The mechanisms by which hbl-1 is positively regulated have not yet been full defined. Currently, this positive regulation seems to be the responsibility of the conserved developmental regulator lin-28. lin-28 is purported to oppose the activities of the 3 let-7 miRNAs and the Caenorhabditis specific heterochronic gene lin-46. Here I demonstrate the removal of 3 let-7 miRNA binding sites in 3’UTR of hbl-1 does not abolish negative regulation of hbl-1 in seam cells. I find lin-28 negatively regulates lin-46 expression by direct binding of the 5’UTR of lin-46. I report a novel sterilely phenotype due to the loss of HBL-1 activity in postembryonic development. Due to the increased sensitivity of the somatic gonad to HBL-1 protein levels, I utilize the development of this tissue as an alternate means to study the genetic relationships between lin-28, lin-46 and hbl-1. My results suggest lin-28 acts through a branched pathway, partially bypassing lin-46 to positively regulate hbl-1 either through its 3’UTR or by targeting a third unknown factor.
Minutillo, Madeleine, "Dual Mechanisms Implemented by LIN-28 for Positive Regulation OF HBL-1 Are Necessary for Proper Development of Distinct Tissues in Caenorhabditis elegans" (2022). Graduate School of Biomedical Sciences Theses and Dissertations. 35.