Biology subjects

Dent, C.

Publications and source records attributed to Dent, C..

3 recordsLinked to original sources

bioRxiv2025

Placental insufficiency causes fetal growth restriction in mice lacking Delta-like homologue 1

Fetal growth restriction (FGR) affects between 3-7% of pregnancies, is associated with increased perinatal morbidity and mortality, and linked to failure of placental function. The placenta is the key transient organ in pregnancy that directs nutrient transfer, intermediary metabolism and the production of hormones that drive maternal metabolic adaptations essential for pregnancy and lactation. The exchange surface of the placenta is formed in early development by the interaction between trophoblast cells that enclose the maternal blood and extraembryonic mesodermal cells that comprise the fetal vasculature. Despite recent insights into trophoblast development derived from novel in-vitro approaches, the processes driving extraembryonic mesoderm development are not well explored. This is due to a dearth of studies employing unbiased approaches to interrogate extraembryonic mesoderm cell populations. Here we use genetic labelling techniques to separate molecular events occurring in the trophoblast from those in the mesodermal layers of the placenta. In combination with conditional targeting, we show that the imprinted gene Dlk1 is a key player in providing nutrients to the embryo by controlling the placental surface area available for nutrient exchange, and by modulating the production of placental hormones that promote maternal nutrient provision in pregnancy.

developmental biology↗

bioRxiv2025

Mutations of short tandem repeats explain abundant trait heritability in Arabidopsis

Short tandem repeats (STRs) mutations are one of the most important fuels of evolution, but are often largely ignored despite their huge effects on phenotypic variations. Here, we leveraged seven Arabidopsis mutation accumulation lines to assess the STR mutation rate, which ranged from 1.93x10-2 to 4.40x10-3 per STR locus per generation and was much higher than the common SNP mutation rate at the level of 10-9-10-8. Interspecific comparison revealed rapid STR turnover, with a large proportion (71.8%) only present in Arabidopsis. In addition, intraspecific comparison of the ten assembled Arabidopsis genomes revealed that 29.3% of STRs were presence/absence variation (PAV), 36.5% of STRs were length variation (LV), 13.0% of STRs were no variation (NV) and the 21.1% STR loci with both LV and PAV. Based on 413 RNA-seq datasets, we identified that length variation of 3,871 STR loci (eSTRs) was associated with gene expression and 651 STR loci (sSTRs) were associated with splicing variation, and over one thousand eSTRs or sSTRs were linked with published genome-wide association study signals. In addition, a direct association between STR length variation and phenotypic variation uncovered a series of STR-trait associations. More notably, using the expression levels of 24,175 genes, the splice strength values of 12,784 splice sites, and 16 phenotypes of natural Arabidopsis populations, we revealed that the STR heritability is 0.111, 0.143 and 0.101, respectively. Overall, our results not only revealed the evolutionary dynamics of STRs, but highlighted the importance of STR variations as an important contributor to missing heritability in the regulation of complex traits.

evolutionary biology↗

bioRxiv2021

MOV10 facilitates messenger RNA decay in an N6-methyladenosine (m6A) dependent manner to maintain the mouse embryonic stem cells state

N6-methyladenosine (m6A) is the most predominant internal mRNA modification in eukaryotes, recognised by its reader proteins (so-called m6A-readers) for regulating subsequent mRNA fates -- splicing, export, localisation, decay, stability, and translation -- to control several biological processes. Although a few m6A-readers have been identified, yet the list is incomplete. Here, we identify a new m6A-reader protein, Moloney leukaemia virus 10 homologue (MOV10), in the m6A pathway. MOV10 recognises m6A-containing mRNAs with a conserved GGm6ACU motif. Mechanistic studies uncover that MOV10 facilitates mRNA decay of its bound m6A-containing mRNAs in an m6A-dependent manner within the cytoplasmic processing bodies (P-bodies). Furthermore, MOV10 decays the Gsk-3{beta} mRNA through m6A that stabilises the {beta}-CATENIN expression of a WNT/{beta}-CATENIN signalling pathway to regulate downstream NANOG expression for maintaining the mouse embryonic stem cells (mESCs) state. Thus, our findings reveal how a newly identified m6A-reader, MOV10 mediates mRNA decay via m6A that impact embryonic stem cell biology.

biochemistry↗