# Endocytic Regulation of Intestinal Development

> **NIH NIH R01** · UNIVERSITY OF ARIZONA · 2021 · $414,725

## Abstract

Endocytic regulation of intestinal development
The intestinal mucosa is a highly differentiated epithelial barrier that is fundamental for normal function of the
intestine. Vesicular trafficking is now recognized as an essential regulator of epithelial polarity, integrity and cell
differentiation, and studies in model systems have shown that endocytosis and membrane trafficking are
essential for normal ontogenesis of the intestine. During development, the epithelial cells of the intestine go
through an intensely endocytic stage that precedes the acquisition of mature intestinal architecture. We
identified endotubin (EDTB) as a highly conserved integral membrane protein in the endocytic complex of
the developing intestine. In vitro, EDTB regulates tight junction assembly and contact-mediated inhibition
of proliferation. In addition, it binds the small GTPase Rab14, which regulates trafficking between
endosomes and the apical plasma membrane. However the role of EDTB during development is
completely unknown. We have generated an intestinal epithelial cell-specific EDTB knockout mouse and,
in Preliminary Data, show that EDTB knockout early in development results in aberrant ontogenesis of
the neonatal intestine, including loss of the apical endocytic complex, intracellular accumulation of apical
plasma membrane proteins, and an aberrant brush border. We will use this EDTB conditional knockout
mouse, together with enteroid cultures and cell lines, to identify the mechanistic basis for these changes
in epithelial differentiation. We will define the mechanisms for interaction with tight junction proteins and
define the domains of EDTB that mediate its effects. Also, we will analyze the role of Rab14 using
intestinal enteroid cultures and human intestinal epithelial cell lines. Finally, we will examine the signaling
pathways known to impact intestinal differentiation and define their interaction with EDTB and apical
endosomes. Collectively, these studies will provide insight into the cellular mechanisms of intestinal
development, which is essential for our understanding of intestinal function. When completed, the experiments
outlined in this proposal will define the role of vesicular trafficking in normal growth, development, and homeostasis
of the intestinal epithelium. This fundamental knowledge will have implications for our understanding of intestinal
disease, both in neonates and adults, and could lay the groundwork for therapeutic targets.

## Key facts

- **NIH application ID:** 10104477
- **Project number:** 5R01DK109701-05
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** Jean M Wilson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $414,725
- **Award type:** 5
- **Project period:** 2017-02-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10104477

## Citation

> US National Institutes of Health, RePORTER application 10104477, Endocytic Regulation of Intestinal Development (5R01DK109701-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10104477. Licensed CC0.

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