# ROLE OF EXTRACELLULAR MATRIX IN MORPHOGENESIS

> **NIH NIH R01** · HARVARD MEDICAL SCHOOL · 1993 · $227,301

## Abstract

The overall aim of the next 5 years of this long standing grant is to learn
how cells migrate on or through extracellular matrix (ECM) and to decipher
the rules governing epithelial-mesenchymal transformation in ECM.

I.  Mesenchymal cell migration.  We seek to prove the theory that the actin
cortex is fixed to ECM substrate during cell migration and the myosin-rich
endoplasm, containing cell organelles, microtubules, and intermediate
filaments, slides past membrane-bound actin into newly forming leading
edge.  (1) The actin cortex and outer surface of the plasmalemma will be
labeled in the living fibroblast by appropriate markers, such as
fluorescent phalloidin and antibodies to ECM receptors, and their locations
monitored by external reference markers during forward movement.  (2) We
will seek additional evidence for the fixed cortex theory by labelling the
endoskeleton and watching it move in relation to the cell surface.

II.  Epithelial-mesenchymal transformation in collagen gels.  (1) We wish
to prove that the fixed cortex motility mechanism is operating during
epithelial-mesenchymal transformation.  We will show that new actin front
end is continuously forming when a mesenchymal cell leaves an epithelium,
and that part of the trailing end remains attached to former epithelial
neighbors in patches.  We will use polarized virus budding and labeled ECM
receptors to see if new membrane is being added to front end.  (2) We will
use in situ hybridization to determine changes in ECM and cytoskeletal gene
transcription during epithelial-mesenchymal transformation.  We expect
vimentin mRNA to appear before cells elongate, actin mRNA to move to the
front end as the cells elongate and type I collagen to be activated after
the cell is bipolar.

III.  Epithelial-mesenchymal transformation in the embryo.  (1) We will
analyze ECM and ECM receptors of the early embryo and correlate their
production with the onset of neural crest and sclerotome formation.  We
will use in situ hybridization to localize their mRNAs.  (2) We will use
carboxyfluorescein to discover novel locations of epithelial-mesenchymal
transformation during embryonic tissue remodeling.

The immediate health relevance is to our understanding of normal
development, but the work could give insights into the causes of congenital
anomalies and abnormal tissue organization, as for example in cataracts,
cleft palate, and cancer.

## Key facts

- **NIH application ID:** 2194340
- **Project number:** 5R01HD000143-33
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **SAM.gov UEI:** JDLVAVGYJQ21
- **Principal Investigator:** ELIZABETH D HAY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $227,301
- **Award type:** 5
- **Project period:** 1975-05-01 → 1994-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2194340

## Citation

> US National Institutes of Health, RePORTER application 2194340, ROLE OF EXTRACELLULAR MATRIX IN MORPHOGENESIS (5R01HD000143-33). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2194340. Licensed CC0.

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