Biology subjects

Vilotte, J.-L.

Publications and source records attributed to Vilotte, J.-L..

3 recordsLinked to original sources

bioRxiv2023

Modeling the critical MCOR-causing deletion in mouse unveils aberrant Sox21 expression in developing and adult iris and ciliary body, and implicates Tgfb2 in MCOR-associated glaucoma and myopia.

Congenital microcoria (MCOR) is a rare hereditary developmental defect of the iris dilator muscle, frequently associated with high axial myopia and high intraocular pressure (IOP) glaucoma. The condition is caused by submicroscopic rearrangements of chromosome 13q32.1. However, the mechanisms underlying the failure of iris development and the origin of associated features remain elusive. Here, we present a 3D architecture model of the 13q32.1 region, demonstrating that MCOR-related deletions consistently disrupt the boundary between two Topologically Associating Domains (TADs). Deleting the critical MCOR-causing region in mice reveals ectopic Sox21 expression precisely aligning with Dct, each located in one of the two neighbor TADs. This observation is consistent with the TADs boundary alteration and adoption of Dct regulatory elements by the Sox21 promoter. Additionally, we identify Tgfb2 as a target gene of SOX21 and show TGFB2 accumulation in the aqueous humor of a MCOR-affected subject. Accumulation of TGFB2 is recognized for its role in glaucoma and potential impact on axial myopia. Our results highlight the importance of SOX21-TGFB2 signaling in iris development and control of eye growth and IOP. Insights from MCOR studies may provide therapeutic avenues for this condition but also for glaucoma and high myopia conditions, affecting millions of people.

genetics↗

bioRxiv2023

Sixteen oogenesin genes are dispensable for fertilityWhat is the significance of the dispensability of genes expressed in germ-cell?

Gene knockout experiments have shown that many genes are dispensable for a given biological function. The Oogenesin/Pramel family contains almost 85 paralogs, about thirty of which are specific to female (as well as male for some of them) germ cells. In this paper, we show that the deletion of a block of around 1Mb containing sixteen paralogous genes of the Oogenesin/Pramel family specific to germ cells, including Oogenesin-2, -3 and -4, has no consequences on fertility or prolificacy in mouse both sexes. The dispensability of these genes is probably due to the compensation by the other germ-cell specific paralogs.

molecular biology↗

bioRxiv2021

Potential genetic robustness of Prnp and Sprn double knockout mouse embryos towards ShRNA-lentiviral inoculation

Shadoo, encoded by Sprn, and PrP, encoded by Prnp, are related proteins whose biological functions are still incompletely understood. Although previous knockdown experiments have suggested the necessity of Shadoo in the absence of PrP during early mouse embryogenesis, little impact of the double-knockout of these two loci was reported. To further investigate this apparent discrepancy, we compared the transcriptome of WT, Prnp0/0 and Prnp0/0, Sprn0/0 E6.5 mouse embryos following inoculation by Sprn-ShRNA or Prnp-ShRNA lentiviral vectors at the one-cell stage. Our results highlighted a significant induction of an apoptotic pathway in Prnp0/0 E6.5 mouse embryos inoculated with Sprn-ShRNA vectors alongside interferon and to a lesser extent inflammatory responses, confirming previous reported experiments. On the contrary, ShRNA vector inoculation in Prnp0/0, Sprn0/0 embryos did not induce apoptosis and resulted in lower interferon responses. Finally, comparisons of the transcriptome of WT and Prnp0/0, Sprn0/0 embryos revealed only slight differences, which may in part explain the genetic robustness observed in the latter genotype. HighlightsO_LISprn-ShRNA lentivirus vector inoculation in Prnp knockout one-cell mouse embryos results in the induction of an apoptosis pathway at E6.5, alongside interferon and to a lesser extent inflammatory responses. C_LIO_LISprn- or Prnp-ShRNA lentivirus vector inoculations in Prnp/Sprn knockout one-cell mouse embryos induce lower interferon responses and no apoptotic pathway at E6.5. C_LIO_LIAlthough wild type and Prnp/Sprn knockout E6.5 mouse embryos are transcriptomically similar, some differences might explain this apparent resilience of the double knockout genotype. C_LI

genomics↗