C-terminal binding proteins (CtBPs) are transcriptional co-repressors involved in many biological processes, including neuronal development. Their loss results in embryonic lethality or gross neurodevelopmental defects in mice and Drosophila. In Caenorhabditis elegans, reduction ofctbp-1 function disrupts development of the dorsal SMD (SMDD) axon, with the axon leaving the dorso-lateral path along which it normally extends.
Analysis of two sets of microarray data that compared transcript enrichment between young adult wild-type and two ctbp-1 mutant strains revealed that 48 genes were consistently upregulated by more than 2-fold in the ctbp-1 mutant strains. As CTBP-1 is expressed in both the nervous system and hypodermis, 12 candidate direct target genes expressed in either tissue were selected from amongst the 48 genes. Further examination for possible mechanistic links to axon guidance revealed that 4 were Hedgehog-related genes—wrt-6, wrt-10, grl-5 and grl-16. The roles of these Hedgehog-related genes are relatively unexplored, but similar factors in other model organisms have been implicated in neuronal development and more recently in C. elegans by Riveiro et al. (2017), who demonstrated that wrt-8 and grl-16 influence PVQ axon migration.
This project investigates how CTBP-1 regulates SMDD development by characterizing the expression of the 4 Hedgehog-related genes and examining if their over-expression could be responsible for the misguided SMDD axon phenotype displayed by ctbp-1 mutants. Previously, Aspöck et al. (1999) and Hao et a. (2006) reported on the expression profiles of wrt-6, wrt-10 and grl-5, but did not detect expression of grl-16 from a reporter. We have successfully generated transcriptional reporter lines for the 4 Hedgehog-related genes and have begun characterizing where these genes are expressed in wild-type and whether that expression is influenced by loss of ctbp-1 function. We will additionally report our progress towards determining the effect of over-expression of the Hedgehog-related genes on SMDD development.
|Number of pages
|Published - Oct 2017
|ACeS 2017 The inaugural Australian C. elegans Symposium - University of Queensland, Brisbane, Australia
Duration: 25 Oct 2017 → 27 Oct 2017
|ACeS 2017 The inaugural Australian C. elegans Symposium
|25/10/17 → 27/10/17