DPFF‐1 transcription factor deficiency causes the aberrant activation of MPK‐1 and meiotic defects in the Caenorhabditis elegans germline

Abstract

The d4 family of transcription factors consists of three members in mammals. DPF1/neuro-d4 is expressed mainly in neurons and the peripheral nervous system, and is important for brain development. DPF2/requiem/ubi-d4 is expressed ubiquitously and presumably functions as an apoptotic factor, especially during the deprivation of trophic factors. DPF3/cer-d4 is expressed in neurons and in the heart, and is important for heart development and function in zebrafish. In Drosophila, there is only one member, dd4, whose function is still unknown, but it is expressed in many tissues and is particularly abundant in the brain of developing embryos and in adults. Here, we present DPFF-1, the only member of this family of proteins in the nematode C. elegans. DPFF-1 is similar to its mammalian homolog DPF2/requiem/ubi-d4 because it is ubiquitously expressed during embryogenesis and in adult tissues, and because it is important for the induction of germ cell apoptosis during stress. Here, we show that dpff-1 null mutant animals produce less progeny than wild-type nematodes, presumably due to meiotic defects. Gonads of dpff-1 deficient animals showed more germ cells in pachytene and overexpressed the P-MPK-1 signal. Additionally, these animals presented higher levels of p53-induced germ cell apoptosis than wild-type animals. Furthermore, we observed that dpff-1 deficient animals are more sensitive to heat shock. This is the first report showing that the d4 family of transcription factors could be involved in meiosis and stress protection.

Rilmenidine extends lifespan and healthspan in Caenorhabditis elegans via a nischarin I1‐imidazoline receptor

“…C. elegans contains only one ERK gene ( mpk‐1 ), rendering it the more facile and reliable system in the pathway to measure compared to the six isoforms of PLC. The activation of MPK‐1 was measured, by way of pMPK‐1 to α‐tubulin immunoreactivity, in response to 24 h treatment with rilmenidine at varying concentrations (200, 300, and 400 μM) as per (Chen et al, 2008 ; Villanueva‐Chimal et al, 2017 ) (Figure S4D ). Rilmenidine increased MPK‐1 phosphorylation the strongest at the concentration of 200 μM; the same concentration that elicits the greatest prolongevity effect.…”

SOX11 variants cause a neurodevelopmental disorder with infrequent ocular malformations and hypogonadotropic hypogonadism and with distinct DNA methylation profile

“…Many of these DMPs have regulatory roles in neural differentiation and are associated with NDDs (ie, family with sequence similarity 160 member B1 [FAM160B1] 36 and FMN2 37 ). Some DMPs have regulatory role in the epigenetic machinery, such as DPF1 38 and AHCTF1. 39 This highlights the fact that aberrations in the expression/methylation status of SOX11 affects expression/ methylation status of genes involved in neural differentiation and/or epigenetic machinery, in agreement with the observed global hypomethylation seen in Supplemental Figure 5.…”

Caenorhabditis elegans respond to high-glucose diets through a network of stress-responsive transcription factors

“…Approximately 200 L1 larvae from Psod-3 :: gfp synchronized animals were seeded on 60 mm plates of NGM media supplemented with 0, 20, 40, 80 or 100 mM glucose and incubated at 20°C until they reached L4 larval stage. At this stage plates were transferred to an air incubator at 31°C for 8 h as indicated [ 29 ]. After heat shock, animals were anesthetized with 10 mM tetramisole, mounted on agarose pads at 2% and observed on a Nikon Eclipse E600 microscope equipped with an AxioCam MRc camera and Zeiss AxioVision software.…”