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Epigenetic factors Dnmt1 and Uhrf1 coordinate intestinal development
Julia Ganz1, Ellie Melancon1, Catherine Wilson1
1Institute of Neuroscience, 1254 University of Oregon, Eugene, OR, 97403, USA.
Developmental Biology
|August 9, 2019
Summary
Loss of Uhrf1 disrupts intestinal development by affecting ectoderm-derived neurons and mesoderm-derived smooth muscle. Uhrf1 and Dnmt1 work together in the development of the enteric nervous system and intestinal muscle.
Area of Science:
- Developmental biology
- Epigenetics
- Gastroenterology
Background:
- Intestinal tract development involves complex signaling between cells from all three germ layers.
- Epigenetic modifications are crucial for endoderm-derived intestinal epithelium development.
- The role of epigenetic regulators in the development of other intestinal cell types is not well understood.
Purpose of the Study:
- To investigate the role of epigenetic modifications in the development of non-endodermal intestinal cell types.
- To determine the function of ubiquitin-like protein containing PHD and RING finger domains 1 (uhrf1) in intestinal development.
- To explore the potential link between uhrf1, Dnmt1, and Hirschsprung disease.
Main Methods:
- Utilized genetic chimeras to study cell-autonomous and non-autonomous functions of Uhrf1.
- Generated and analyzed uhrf1 and dnmt1 single and double mutants.
- Examined the effects of uhrf1 and dnmt1 loss on enteric neuron and intestinal smooth muscle development.
Main Results:
- Functional loss of uhrf1 led to reduced enteric neurons and disrupted intestinal smooth muscle.
- Uhrf1 functions both cell-autonomously in neuron precursors and cell-non-autonomously in surrounding cells.
- Dnmt1 and Uhrf1 function together in enteric neuron and intestinal muscle development, with double mutants showing similar phenotypes to single mutants.
Conclusions:
- Epigenetic regulators like uhrf1 are essential for coordinating intestinal tract development.
- This study provides the first evidence that epigenetic genes influence the development of the enteric nervous system (ENS).
- Uhrf1 and Dnmt1 are identified as potential candidates for Hirschsprung disease.
Keywords:
DNA methylationEnteric nervous systemHirschsprung diseaseIntestinal developmentIntestinal epitheliumIntestinal smooth muscleMore Related Videos
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