A novel fibroblast growth factor gene expressed in the developing nervous system is a downstream target of the chimeric homeodomain oncoprotein E2A-Pbx1

J R McWhirter; M Goulding; J A Weiner; J Chun; C Murre

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A novel fibroblast growth factor gene expressed in the developing nervous system is a downstream target of the chimeric homeodomain oncoprotein E2A-Pbx1

Journal article

Peer reviewed

A novel fibroblast growth factor gene expressed in the developing nervous system is a downstream target of the chimeric homeodomain oncoprotein E2A-Pbx1

J R McWhirter, M Goulding, J A Weiner, J Chun and C Murre

Development (Cambridge), Vol.124(17), pp.3221-3232

09/1997

PMID: 9310317

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Abstract

Pbx1 is a homeodomain transcription factor that has the ability to form heterodimers with homeodomain proteins encoded by the homeotic selector (Hox) gene complexes and increase their DNA-binding affinity and specificity. A current hypothesis proposes that interactions with Pbx1 are necessary for Hox proteins to regulate downstream target genes that in turn control growth, differentiation and morphogenesis during development. In pre B cell leukemias containing the t(1;19) chromosome translocation, Pbx1 is converted into a strong transactivator by fusion to the activation domain of the bHLH transcription factor E2A. The E2A-Pbx1 fusion protein should therefore activate transcription of genes normally regulated by Pbx1. We have used the subtractive process of representational difference analysis to identify targets of E2A-Pbx1. We show that E2A-Pbx1 can directly activate transcription of a novel member of the fibroblast growth factor family of intercellular signalling molecules, FGF-15. The FGF-15 gene is expressed in a regionally restricted pattern in the developing nervous system, suggesting that FGF-15 may play an important role in regulating cell division and patterning within specific regions of the embryonic brain, spinal cord and sensory organs.

Brain - embryology

Oncogene Proteins, Fusion - metabolism

Spinal Cord - metabolism

Homeodomain Proteins - metabolism

Transcriptional Activation

DNA, Complementary - genetics

Fibroblast Growth Factors - genetics

Molecular Sequence Data

DNA Primers - genetics

Central Nervous System - embryology

Brain - metabolism

Central Nervous System - growth & development

In Situ Hybridization

Gene Expression Regulation, Developmental

Base Sequence

Cloning, Molecular

Polymerase Chain Reaction

Amino Acid Sequence

Promoter Regions, Genetic

Binding Sites - genetics

Homeodomain Proteins - genetics

Sequence Homology, Amino Acid

Spinal Cord - embryology

Animals

Oncogene Proteins, Fusion - genetics

Mice

Details

Title: Subtitle: A novel fibroblast growth factor gene expressed in the developing nervous system is a downstream target of the chimeric homeodomain oncoprotein E2A-Pbx1
Creators: J R McWhirter - Department of Biology, School of Medicine, University of California, San Diego, La Jolla 92093, USA
M Goulding
J A Weiner
J Chun
C Murre
Resource Type: Journal article
Publication Details: Development (Cambridge), Vol.124(17), pp.3221-3232
PMID: 9310317
NLM abbreviation: Development
ISSN: 0950-1991
eISSN: 1477-9129
Publisher: England
Language: English
Date published: 09/1997
Academic Unit: Liberal Arts and Science Admin; Psychiatry; Iowa Neuroscience Institute; Biology
Record Identifier: 9983997418202771

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209 Times Cited - Web of Science