Shaping segments: Hox gene function in the genomic age

Abstract

Despite decades of research, morphogenesis along the various body axes remains one of the major mysteries in developmental biology. A milestone in the field was the realisation that a set of closely related regulators, called Hox genes, specifies the identity of body segments along the anterior-posterior (AP) axis in most animals. Hox genes have been highly conserved throughout metazoan evolution and code for homeodomain-containing transcription factors. Thus, they exert their function mainly through activation or repression of downstream genes. However, while much is known about Hox gene structure and molecular function, only a few target genes have been identified and studied in detail. Our knowledge of Hox downstream genes is therefore far from complete and consequently Hox-controlled morphogenesis is still poorly understood. Genome-wide approaches have facilitated the identification of large numbers of Hox downstream genes both in Drosophila and vertebrates, and represent a crucial step towards a comprehensive understanding of how Hox proteins drive morphological diversification. In this review, we focus on the role of Hox genes in shaping segmental morphologies along the AP axis in Drosophila, discuss some of the conclusions drawn from analyses of large target gene sets and highlight methods that could be used to gain a more thorough understanding of Hox molecular function. In addition, the mechanisms of Hox target gene regulation are considered with special emphasis on recent findings and their implications for Hox protein specificity in the context of the whole organism.

The H3K27me3 Demethylase dUTX Is a Suppressor of Notch- and Rb-Dependent Tumors in Drosophila

“…The epigenetic control of gene expression has been best studied for the control of homeotic gene expression (33,57), which is established during embryogenesis and maintained throughout animal life. However, not only homeotic genes are regulated through epigenetic modifications.…”

“…The best-characterized targets of H3K27me3/Pc-mediated silencing are homeotic genes, which are critical regulators of animal patterning (33,57). However, many other genes are also enriched for H3K27 methylation and Pc binding (5,6,45,53,65,72,76).…”

Hox gene Ultrabithorax regulates distinct sets of target genes at successive stages of Drosophila haltere morphogenesis

“…Our genome-wide study provides a firm demonstration of a view previously suggested by genetics that Ubx is a micromanager in the haltere: it modulates the wing program by interacting with the wing transcriptional network at multiple levels and over many developmental stages, controlling the expression of numerous target genes with a wide range of functions. However, there is also evidence for other modes of Hox gene action (4)(5)(6)(7)(8). For example, the role of Abdominal B in Drosophila posterior spiracles is more akin to that of a master control gene (30).…”

“…It has been further complicated by the functional redundancy of the Hox proteins and the cross-regulatory interactions between them. These factors have made it difficult to elucidate the complete set of target genes modulated by any one Hox gene over the course of a single developmental process (3)(4)(5)(6)(7)(8). Thus, it remains an open question of how these widely conserved patterning genes link to the actual effectors of cell and organ morphology at a genome-wide level over time.…”

Muscle wasted: a novel component of theDrosophilahistone locus body required for muscle integrity

“…Some PAH-repeat-containing proteins are known to function as components of co-repressor complexes in transcriptional silencing (Wang et al, 1990). SANT and homeodomains function in the regulation of transcription (Boyer et al, 2004;Hueber and Lohmann, 2008). Interestingly, BLAST searches revealed that the PAH repeats of Mute-L are 28% identical to that of zebrafish Ugly duckling (Udu), a nuclear protein required for somite development (Lim et al, 2009;Liu et al, 2007) and 27% identical to that of human GON4L or YARP (YY1AP-related protein 1), a nuclear protein with suggested transcriptionalregulator-like functions (supplementary material Fig.…”