ExdHth

ExdHth refers to the functional transcriptional cofactor complex formed by the Drosophila proteins Extradenticle (Exd) and Homothorax (Hth). This heterodimer acts as a cofactor for Hox proteins, expanding their DNA-binding specificity and enabling proper patterning along the proximal–distal axis during embryogenesis and in imaginal discs.

Exd and Hth are both TALE-class homeobox factors that interact to form the Exd/Hth complex, which can be recruited by Hox proteins to target enhancers. In many cells, Hth promotes the nuclear localization of Exd, enabling the formation of the active complex. The Exd/Hth heterodimer, often in conjunction with Hox proteins, binds DNA and modulates transcription of genes involved in segmental identity and appendage formation.

The Exd/Hth module is evolutionarily conserved as a cofactor system; in vertebrates, the homologous proteins Meis (Hth) and Pbx (Exd) serve as cofactors for HOX transcription factors, reflecting a shared mechanism for specifying gene expression patterns during development.

Functional roles of ExdHth include regulation of proximal–distal identity in limbs and other structures, contributing to correct appendage patterning and segmentation. Genetic and molecular studies show that Exd/Hth activity interacts with multiple Hox genes to fine-tune target gene expression, and disruptions can lead to mispatterning or homeotic transformations.

In summary, ExdHth is a key transcriptional cofactor complex in Drosophila that partners with Hox proteins to control developmental patterning, with a deeply conserved mechanism mirrored by vertebrate Pbx-Meis-HOX interactions.