# MOLECULAR ANALYSIS OF DEVELOPMENT-REGULATING GENES

> **NIH NIH R01** · STANFORD UNIVERSITY · 1994 · $254,676

## Abstract

Our goal is to learn the molecular mechanisms by which genes control the
development of multicellular structures.  Homeotic genes are among the most
important regulators of pattern formation, mutations in them causing
dramatic transformations of one part of an animal into the likeness of
another part.  Different alleles of the Drosophila Antennapedia (Antp)
homeotic gene, for example, transform antennae into legs, legs into
antennae, or eyes into wings. The homeotic genes are master regulators,
coordinating the transcription of other genes to control morphogenesis
during embryonic development and metamorphosis.

The precise spatial and temporal patterns of transcription of homeotic
genes are crucial for directing cells into different developmental
pathways.  The patterns are initiated under the control of segmentation
genes and are then maintained and modified by interactions among the
homeotic genes and by Polycomb group and other genes.  We are using
promoter-lacZ gene fusions, introduced into flies, to investigate the
regulation of the two Antp promoters.  We will search specifically for
cis-acting Antp sequences regulated by known segmentation genes and for
sequences involved in maintaining precise patterns of expression.

The protein products of homeotic genes are transcription factors but little
is known about the "target" genes regulated by the homeotic proteins.  We
have found that two growth factor-like proteins, encoded by the dpp and wg
genes, are regulated by homeotic genes.  To obtain additional information
about target genes we will take advantage of a powerful new tool, the
localization of homeotic proteins on polytene chromosomes in vivo.
Homeotic proteins with very similar DNA binding domains direct the
formation of very different segments of the fly.  Our in vivo assays reveal
the different homeotic proteins distributed in distinct patterns on the
polytene chromosomes, demonstrating a high degree of specificity and
suggesting that the proteins control different arrays of target genes.  One
putative target gene identified in this way is in fact regulated by the
homeotic protein which binds there.  By transposing fragments of the target
gene DNA to new chromosomal sites the sequences to which the homeotic
protein binds can be mapped.  The polytene assay as well as biochemical
methods will be used to answer four questions: What DNA sequences are
regulated by the different homeotic proteins?  Are known gene interactions,
such as cross-regulation among the homeotic genes and the regulation of the
growth factors dpp and wg, due to direct protein-DNA interactions?  What
aspects of the proteins' structures are essential for determining the
specificity of the proteins' interactions with their targets?  What are
some of the target genes and how do they contribute to morphogenesis?
These studies will lead to a better understanding of the transcriptional
control of morphogenesis.

## Key facts

- **NIH application ID:** 2197579
- **Project number:** 5R01HD018163-12
- **Recipient organization:** STANFORD UNIVERSITY
- **SAM.gov UEI:** HJD6G4D6TJY5
- **Principal Investigator:** Matthew P. Scott
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $254,676
- **Award type:** 5
- **Project period:** 1983-09-01 → 1996-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2197579

## Citation

> US National Institutes of Health, RePORTER application 2197579, MOLECULAR ANALYSIS OF DEVELOPMENT-REGULATING GENES (5R01HD018163-12). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2197579. Licensed CC0.

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