Epigenetic factors Dnmt1 and Uhrf1 coordinate intestinal development

Developmental Biology
J GanzJ S Eisen

Abstract

Intestinal tract development is a coordinated process involving signaling among the progenitors and developing cells from all three germ layers. Development of endoderm-derived intestinal epithelium has been shown to depend on epigenetic modifications, but whether that is also the case for intestinal tract cell types from other germ layers remains unclear. We found that functional loss of a DNA methylation machinery component, ubiquitin-like protein containing PHD and RING finger domains 1 (uhrf1), leads to reduced numbers of ectoderm-derived enteric neurons and severe disruption of mesoderm-derived intestinal smooth muscle. Genetic chimeras revealed that Uhrf1 functions both cell-autonomously in enteric neuron precursors and cell-non-autonomously in surrounding intestinal cells, consistent with what is known about signaling interactions between these cell types that promote one another's development. Uhrf1 recruits the DNA methyltransferase Dnmt1 to unmethylated DNA during replication. Dnmt1 is also expressed in enteric neurons and smooth muscle progenitors. dnmt1 mutants have fewer enteric neurons and disrupted intestinal smooth muscle compared to wildtypes. Because dnmt1;uhrf1 double mutants have a similar phenotype to dnmt1...Continue Reading

Citations

Feb 9, 2021·Frontiers in Cell and Developmental Biology·Laura E KuilMaria M Alves
Jul 12, 2021·Seminars in Perinatology·Robert C PeeryLanlan Shen
Oct 5, 2021·Genome Génome / Conseil National De Recherches Canada·Ayse Gokce KeskusOzlen Konu
Nov 26, 2021·European Journal of Histochemistry : EJH·Francesca BiancoRoberto De Giorgio

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