The folic acid metabolism gene mel-32/Shmt is required for normal cell cycle lengths in Caenorhabditis elegans

Abstract

Neural tube defects are common and serious birth defects in which the brain and/or spinal cord are exposed outside the body. Supplementation of foods with folic acid, an essential vitamin, is linked to a lower risk of neural tube defects; however, the mechanisms by which folic acid influence neural tube defect risk are unclear. Our research seeks to identify the basic cellular roles of known folic acid metabolism genes during morphogenesis using the roundworm Caenorhabditis elegans (C. elegans) as a simple model system. Here, we used live imaging to characterize defects in embryonic development when mel-32 is depleted. mel-32 is an essential folic acid metabolism gene in C. elegans and a homolog to the mammalian enzyme serine hydroxymethyltransferase (Shmt). Disruption of mel-32 resulted in a doubling or tripling of cell cycle lengths and a lack of directed cell movement during embryogenesis. However, the order of cell divisions, as determined by lineage analysis, is unchanged compared to wild type embryos. These results suggest that mel-32/Shmt is required for normal cell cycle lengths in C. elegans.

Effects of Dietary Folic Acid Supplementation on Growth Performance and Immune Parameters in Weanling Piglets

“…Cells lacking folate accumulate in the S phase, leading to increased uracil misincorporation and DNA damage. When folate is reintroduced to folate-deficient cells, S phase accumulation is reversed and proliferation is restored [22,23]. Courtemanche et al (2004) [24] found that folate deficiency was associated with reduced T-cell proliferation, increased apoptosis, a marked decrease of CD8 + cells, an increase of the CD4 + /CD8 + ratio, and that the proliferation of activated CD8 + cells was more sensitive to the lack of folate than CD4 + cells in vitro.…”

Serine hydroxymethyl transferase (Shmt) is required for optic lobe neuroepithelia development in Drosophila

“…Shmt catalyses the reversible reaction from serine to glycine and tetrahydrofolate (THF) to 5,10-methylene THF (meTHF), thus originating one-carbon units necessary for several metabolic reactions in the cell, including the synthesis of nucleotides and generation of universal methyl donor SAM for methylation reactions. Shmt has been shown to have a role in cellular growth and proliferation in mammals, Caenorhabditis elegans and Drosophila ( Kim et al, 2015 ; Konrad et al, 2018 ; Liu et al, 2019 ; Winkler et al, 2017 ). In C. elegans , disruption of the shmt homologue causes an increase in cell cycle length ( Liu et al, 2019 ).…”