# MECHANISM OF GENE REGULATION IN DROSOPHILA DEVELOPMENT

> **NIH NIH R01** · STANFORD UNIVERSITY · 1994 · $216,862

## Abstract

Homeotic genes in Drosophila such as Ultrabithorax (Ubx) and
Antennapedia (Antp) select and maintain the identity of specific
body segments during development, and must therefore be deployed
at specific body positions at particular times in development.  A
regulatory network of about 30 genes, which play early roles on
defining the major body axis and partitioning the animal into
segments, also govern the initial patterns of expression of the
homeotics, and these patterns are subsequently refined by cross-
regulatory interactions between the homeotics.  Maintenance of the
patterns requires the action of another set of genes, the Polycomb
group, and perhaps autoregulatory activities of the homeotics.  The
long term goal of this research is to reconstruct homeotic gene
regulation in vitro from purified components, in order to determine
the biochemical mechanisms of the processes by which gene
expression is initiated, refined, and maintained during
development.

Several regulatory interactions have been recapitulated in a
Drosophila cell culture system.  Using a cotransfection assay in
which a plasmid which express one gene product is introduced into
cultured cells along with a candidate target gene, cross-regulatory
and autoregulatory activities of Antp and Ubx proteins have been
demonstrated.  Also, the regulatory activity of fushi tarazu
protein, the product of a gene involved in segmentation, has been
demonstrated.  Purified Ubx protein binds with high affinity to
sequences in and around Antp and Ubx promoters, suggesting that at
least some of these regulatory effects may be direct and mediated
by protein binding to transcriptional control regions.  The goals
of this project are to determine the mechanism of regulation of
Antp and Ubx expression by an Ubx protein, using a combined in vivo
and in vitro approach and to begin to explore other aspects of
homeotic gene regulation in the cell culture system.  Specifically,
we plan to:

1.  Identify and characterize in detail the cis-acting sites of
regulation of Ubx protein in the Antp and Ubx promoter regions
using the cotransfection assay, and determine the relationship of
these sites to the in vitro binding sites of the protein and to the
regulatory sites of Antp and fushi tarazu proteins.

2.  Evaluate the function of the identified regulatory sites in the
developing animal.

3.  Establish an in vitro system to study regulation of Antp and
Ubx expression by Ubx protein, and begin biochemical fractionation
of the system.

4.  Attempt to reconstruct the combinatorial control of homeotic
gene expression by fushi tarazu and other segmentation genes in the
cell culture system.

## Key facts

- **NIH application ID:** 2190953
- **Project number:** 9R01GM052070-06
- **Recipient organization:** STANFORD UNIVERSITY
- **SAM.gov UEI:** HJD6G4D6TJY5
- **Principal Investigator:** MARK A KRASNOW
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $216,862
- **Award type:** 9
- **Project period:** 1989-04-01 → 1998-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2190953

## Citation

> US National Institutes of Health, RePORTER application 2190953, MECHANISM OF GENE REGULATION IN DROSOPHILA DEVELOPMENT (9R01GM052070-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2190953. Licensed CC0.

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