# REGULATION OF LAMININ GENES BY RETINOIDS

> **NIH NIH R01** · WEILL MEDICAL COLL OF CORNELL UNIV · 1994 · $263,249

## Abstract

Retinoic acid, a vitamin A derivative, is a powerful signalling molecule
that controls aspects of vertebrate cell differentiation nd pattern
formation during embryonic development.  In addition, retinoic acid can
inhibit or reverse the process of neoplastic transformation.  One of the
mechanisms by which retinoic acid (RA) may influence these processes is
via the regulation of the expression of genes encoding constituents of
the basement membrane such as laminin and collagen IV.  Over the past
four years under the auspices of HD24319 we have studied the regulation
of the murine laminin B1 gene by retinoic acid during the differentiation
of cultured murine embryonic stem cells into parietal endoderm, a type
of embryonic epithelial cell.  We have shown that the laminin B1 gene is
transcriptionally activated by 10-fold via an RARE (RA-response element)
in its promoter that binds retinoic acid receptor:RA complexes.  In
addition, we have defined a region in the laminin B1 promoter between -
4.3 and 3.6 kb that enhances transcription.  Finally, we have identified
new molecular markers for the perietal endoderm cells, including F117,
a chondroitin sulfate proteoglycan, and BMP-2.  Both of these genes are
expressed at much higher levels in parietal endoderm than in
undifferentiated stem cells.

Over the next five years we want to understand how the spatial and
temporal regulation of laminin B1 gene expression during embryogenesis
is achieved, and to determine how much of the spatial and temporal
regulation of laminin B1 in the embryo is controlled by retinoic acid via
the RARE.  We will generate various laminin B1 promoter/beta-
galactosidase expression vectors and inject these into fertilized 1-cell
eggs to create transgenic mice that express beta-gal under the control
of various portions of the laminin B1 promoter DNA.  These transgenic
mice will be analyzed to determine if the spatial and temporal regulation
of beta-gal activity (measured by a colorimetric assay) reflects that of
the endogenous laminin B1 gene (measured by in situ hybridization).  We
also plan to generate mice in which the laminin B1 gene is disrupted via
homologous recombination to study the function of laminin B1 in early
embryogenesis.  Finally, we plan to elucidate the mechanism by which RA
regulates the other laminin genes, A and B2, and a chondroitin sulfate
proteoglycan, F117, during F9 embryonic stem cell differentiation.  This
aim will be accomplished by using DNAse I hypersensitivity assays,
promoter/chloramphenicol acetyl transferase constructs in transient
transfection assays of F9 cells +/- RA, gel retardation assays, and
footprinting experiments.  Our studies of the regulation of these
basement membrane genes by retinoic acid should lead to a better
understanding of processes as diverse as cell differentiation,
teratogenesis, cancer metastasis, angiogenesis, and diabetic nephropathy.

## Key facts

- **NIH application ID:** 2199131
- **Project number:** 5R01HD024319-08
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **SAM.gov UEI:** YNT8TCJH8FQ8
- **Principal Investigator:** LORRAINE J GUDAS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $263,249
- **Award type:** 5
- **Project period:** 1988-04-15 → 1998-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2199131

## Citation

> US National Institutes of Health, RePORTER application 2199131, REGULATION OF LAMININ GENES BY RETINOIDS (5R01HD024319-08). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2199131. Licensed CC0.

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