# EXTRACELLULAR MATERIALS AND EMBRYONIC ORGAN FORMATION

> **NIH NIH R37** · BOSTON CHILDREN'S HOSPITAL · 1994 · $252,244

## Abstract

The cellular behavior involved in morphogenesis are regulated by
molecules at cell surfaces that bind cells to the extracellular
matrix and to other cells.  Epithelial cells contain a cell surface
proteoglycan that is a high affinity receptor specific for
interstitial matrix materials.  The proteoglycan appears to
stabilize epithelial sheets by physically linking the intracellular
cytoskeleton with the matrix produced by mesenchymal cells.

Recent results lead to the working hypothesis that the core protein
of the cell surface proteoglycan, the protein to which the
glycosaminoglycan chains are covalently bound, is a developmentally
regulated molecule that functions as a matrix receptor or as a cell
adhesion molecule depending on its post-translational
modifications. As a matrix receptor, it would contain heparan and
chondroitin sulfate chains, be expressed late in development and,
in mature tissues, be solely on the basolateral surface of simple
epithelial cells.  As a cell adhesion molecule, it would be less
extensively glycosylated, be expressed early in development and,
in mature tissues, surround stratified epithelial cells.  During
embryogenesis, it would be present on both epithelial and
mesenchymal cells, but change its expression in association with
morphogenetic events.

This application is designed to explore the hypothesis that the
epithelial cell surface proteoglycan is a developmentally regulated
multifunctional adhesion molecule.  The specific aims are to:

(i)  evaluate the regulation of cell surface proteoglycan
expression in early mouse embryos and during subsequence
morphogenetic events by immunological and molecular assessments of
its time of appearance, cell and tissue localization, post-
translational modifications and mRNA level,

(ii)  test whether the cell surface proteoglycan functions as
a cell adhesion molecule by attempting to perturb cell aggregation
and histogenesis with defined antibodies and ligands, to isolate
an endogenous ligand(s) and comparing its modifications in simple
and stratified epithelia,

(iii)  define the matrix receptor role by examining whether
it traverses the basal lamina, comparing its function with other
receptors, evaluating whether it mediates receptor-specific
cellular responses and generating cells that are deficient or
enhanced in the cell surface proteoglycan.

Knowledge of the mechanisms involved in cell-cell and cell-matrix
adhesion is critically important to an understanding of cell
behavior during development and neoplastic invasion.  This research
will provide new insight into these mechanisms, potentially leading
to diagnosis, treatment and ultimately, prevention of birth defects
and metastases.

## Key facts

- **NIH application ID:** 2194995
- **Project number:** 5R37HD006763-22
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **SAM.gov UEI:** Z1L9F1MM1RY3
- **Principal Investigator:** MERTON R BERNFIELD
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $252,244
- **Award type:** 5
- **Project period:** 1976-05-01 → 1997-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2194995

## Citation

> US National Institutes of Health, RePORTER application 2194995, EXTRACELLULAR MATERIALS AND EMBRYONIC ORGAN FORMATION (5R37HD006763-22). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2194995. Licensed CC0.

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