# Mechanisms of epithelial remodeling during organ development in C. elegans

> **NIH NIH R01** · FRED HUTCHINSON CANCER CENTER · 2020 · $225,176

## Abstract

PROJECT SUMMARY/ABSTRACT
 One of the fundamental steps in the formation of most organs is the assembly of cells
into epithelial layers; simple epithelial cells share a common polarity, are linked by apical
junctions and share a basal basement membrane. Epithelial precursors often arise in
different parts of the embryo and must aggregate together, often sorting from other types
of cells, to form a primordium. Cells within the primordium must then undergo changes
in position or shape to create organ morphology. Some remodeling-specific behaviors of
normal epithelia cells, such as the loss of adhesion, are reminiscent of cancer cells, the
vast majority of which originate from epithelial cells. We want to understand how
epithelial cells sort and rearrange, and are studying this in the digestive tract of the
nematode C. elegans. C. elegans provides a simple genetic system for investigating
basic problems of cell biology, and has had major impact on our understanding of
diverse processes such as apoptosis or RNA-mediated gene inhibition. The digestive
tract consists primarily of two epithelial tubes, the pharynx and the intestine; we will use
the pharyngeal cells to study how precursor cells sort from other cell types, and use the
intestine to study how epithelial cells rearrange during organogenesis. Although the
pharyngeal precursors cells normally arise from contiguous cells, we demonstrated that
they have sorting potential when mixed with other cell types. We want to study the cell
biology of sorting in this model, and identify genes required for sorting. Cells at both
ends of the intestinal tube undergo a rotation during morphogenesis; we believe this
rotation functions to align the lumen throughout the length of the tube. We discovered
that the anterior intestinal cells are guided to their new positions by an UNC-6/netrin
signaling pathway. This pathway is best understood for its function in nervous system
development, but several recent studies have demonstrated that it is also important for
the development of non-neural tissues. We want to determine how this pathway
functions to reposition the anterior cells, and to determine how cells at the posterior end
rotate. Finally, we want to use the powerful genetics of C. elegans to identify genes
required for both kinds of epithelial remodeling.

## Key facts

- **NIH application ID:** 10620371
- **Project number:** 6R01GM098583-09
- **Recipient organization:** FRED HUTCHINSON CANCER CENTER
- **Principal Investigator:** JAMES R PRIESS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $225,176
- **Award type:** 6
- **Project period:** 2011-09-01 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10620371

## Citation

> US National Institutes of Health, RePORTER application 10620371, Mechanisms of epithelial remodeling during organ development in C. elegans (6R01GM098583-09). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10620371. Licensed CC0.

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