FHOD-1 is the only formin inCaenorhabditis elegansthat promotes striated muscle growth and Z-line organization in a cell autonomous manner

Abstract

The striated body wall muscles of Caenorhabditis elegans are a simple model system with wellcharacterized sarcomeres that have many vertebrate protein homologs. Previously, we observed deletion mutants for two formin genes, fhod-1 and cyk-1, developed thin muscles with abnormal dense bodies/sarcomere Z-lines. However, the nature of the cyk-1 mutation necessitated maternal CYK-1 expression for viability of the examined animals. Here, we tested the effects of complete loss of CYK-1 using a fast acting temperature-sensitive cyk-1(ts) mutant.Surprisingly, neither post-embryonic loss of CYK-1 nor acute loss of CYK-1 during embryonic sarcomerogenesis caused muscle defects, suggesting CYK-1 might not play a direct role in muscle development. Consistent with this, examination of cyk-1(∆) mutants re-expressing CYK-1 in a mosaic pattern showed CYK-1 cannot rescue muscle defects in a muscle cell autonomous manner, suggesting muscle phenotypes caused by cyk-1 deletion are likely indirect. Conversely, mosaic re-expression of FHOD-1 in fhod-1(Δ) mutants promoted muscle cell growth, as well as proper Z-line organization, in a muscle cell autonomous manner. As we can observe no effect of loss of any other worm formin on muscle development, we conclude that FHOD-1 is the only formin that directly promotes striated muscle development in C. elegans.

FHOD formin and SRF promote post-embryonic striated muscle growth through separate pathways in C. elegans

“…We used C. elegans as a simple model to investigate whether formins promote transcription by SRF during striated muscle development in vivo. One advantage to using C. elegans is that FHOD-1 is the only endogenous formin that directly promotes BWM growth or sarcomere formation [41], compared to evidence that at least five formins are essential for myofibrillogenesis in cardiomyocyte cell culture [67]. Consistent with the possibility FHOD-1 and SRF might function in the same pathway in C. elegans, previous studies had independently shown worms bearing a fhod-1(Δ) deletion allele and worms bearing an unc-120(hypo) hypomorphic allele of the worm SRF gene, each exhibit thin BWMs [40,44].…”

“…Worm FHOD-1 is expressed in all muscle types and is the only formin that promotes BWM growth in a cell autonomous manner [40,41]. One advantage to the use of C. elegans as a model system is that absence of FHOD-1 is not lethal, unlike loss of FHOD3 in mice, allowing (which was not certified by peer review) is the author/funder.…”

FHOD formin and SRF promote striated muscle development through separate pathways inC. elegans

“…Together, these data suggest mDIA1, mDIA2, and FHOD1 contribute to We used C. elegans as a simple model to investigate whether formins promote transcription by SRF during striated muscle development in vivo. One advantage to using C. elegans is that FHOD-1 is the only endogenous formin that directly promotes BWM growth or sarcomere formation [41], compared to evidence that at least five formins are essential for myofibrillogenesis in cardiomyocyte cell culture [67]. Consistent with the possibility FHOD-1 and SRF might function in the same pathway in C. elegans, previous studies had independently shown worms bearing a fhod-1(Δ) deletion allele and worms bearing an unc-120 (hypo) hypomorphic allele of the worm SRF gene, each exhibit thin BWMs [40,44].…”

“…Worm FHOD-1 is expressed in all muscle types and is the only formin that promotes BWM growth in a cell autonomous manner [40,41]. One advantage to the use of C. elegans as a model system is that absence of FHOD-1 is not lethal, unlike loss of FHOD3 in mice, allowing investigation of the effects of FHOD-1 loss on striated muscle at later stages of development.…”