ABSTRACT
Hox genes code for conserved homeodomain transcription factors, which act as regional regulators for the specification of segmental identities along the anterior-posterior axis in all animals studied. They execute their function mainly through the activation or repression of their downstream genes. We have recently identified a large number of genes to be directly or indirectly targeted by Hox proteins through gene expression profiling in the model organism Drosophila. However, the cell-specific regulation of these downstream genes and the functional significance of the regulation are largely unknown. We have validated and functionally studied many of the newly identified downstream genes of the Hox proteins Deformed (Dfd) and Abdominal-B (Abd-B), and provide evidence that Hox proteins regulate a diverse group of downstream genes, from transcription factors to realisators with major and minor roles during morphogenesis.
Subject(s)
Drosophila Proteins/genetics , Drosophila melanogaster/genetics , Genes, Homeobox , Homeodomain Proteins/genetics , Animals , Drosophila Proteins/metabolism , Drosophila melanogaster/anatomy & histology , Drosophila melanogaster/embryology , Drosophila melanogaster/metabolism , Embryo, Nonmammalian/anatomy & histology , Embryo, Nonmammalian/metabolism , Gene Expression Regulation, Developmental , Homeodomain Proteins/metabolism , In Situ Hybridization , LIM-Homeodomain Proteins , Microfilament Proteins/genetics , Microfilament Proteins/metabolism , Morphogenesis/physiology , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Nuclear Proteins/genetics , Nuclear Proteins/metabolism , Paired Box Transcription Factors/genetics , Paired Box Transcription Factors/metabolism , Transcription Factors/genetics , Transcription Factors/metabolismABSTRACT
Hox proteins play fundamental roles in controlling morphogenetic diversity along the anterior-posterior body axis of animals by regulating distinct sets of target genes. Within their rather broad expression domains, individual Hox proteins control cell diversification and pattern formation and consequently target gene expression in a highly localized manner, sometimes even only in a single cell. To achieve this high-regulatory specificity, it has been postulated that Hox proteins co-operate with other transcription factors to activate or repress their target genes in a highly context-specific manner in vivo. However, only a few of these factors have been identified. Here, we analyze the regulation of the cell death gene reaper (rpr) by the Hox protein Deformed (Dfd) and suggest that local activation of rpr expression in the anterior part of the maxillary segment is achieved through a combinatorial interaction of Dfd with at least eight functionally diverse transcriptional regulators on a minimal enhancer. It follows that context-dependent combinations of Hox proteins and other transcription factors on small, modular Hox response elements (HREs) could be responsible for the proper spatio-temporal expression of Hox targets. Thus, a large number of transcription factors are likely to be directly involved in Hox target gene regulation in vivo.
