Hox genes are the family of transcription factors that play a key role in the patterning of the anterior-posterior axis of all bilaterian animals. These genes display clustered organization and colinear expression. Expression boundaries of individual Hox genes usually correspond with morphological boundaries of the body. Previously, we studied Hox gene expression during larval development of the polychaete Alitta virens (formerly Nereis virens) and discovered that Hox genes are expressed in nereid larva according to the spatial colinearity principle. Adult Alitta virens consist of multiple morphologically similar segments, which are formed sequentially in the growth zone. Since the worm grows for most of its life, postlarval segments constantly change their position along the anterior-posterior axis.

Hox genes are the key determinants of different morphogenetic events in all bilaterian animals. These genes are probably responsible for the maintenance of regenerative capacities by providing positional information in the regenerating animal body. Polychaetes are well known for their ability to regenerate the posterior as well as the anterior part of the body. We have recently described the expression of 10 out of 11 Hox genes during postlarval growth of Alitta (Nereis) virens. Hox genes form gradient overlapping expression patterns, which probably do not contribute to the morphological diversity of segments along the anterior-posterior axis of the homonomously segmented worm. We suggest that this gradient expression of Hox genes establishes positional information along the body that can be used to maintain coordinated growth and regeneration.

The concept of regeneration is intimately associated with ideas about positional information, that is, the distribution of various signals prescribing cells their location in an embryo or an adult organism. Hox genes are perfect candidates for the role of factors creating positional information. Their main function is thought to be regionalization of the embryo and the determination of the anterior/posterior (A/P) axis of the bilaterian body according to the rules of temporal and spatial colinearity. At the same time, Hox genes are also expressed postembryonically and may participate in various processes in the adult body. In particular, Hox genes are involved in regeneration, as shown on animals from different evolutionary clades. During reparation Hox genes are responsible for regionalization and specification of the newly formed structures, which reflects their embryonic role. This is not all, however. Hox transcription patterns in some adult organisms and their expression dynamics after damage suggest that Hox genes are involved in creating positional information in the adult body. This information is necessary for consistent reparation, while its fast reorganization may accelerate the reparative process.

Bilaterian animals operate the clusters of Hox genes through a rich repertoire of diverse mechanisms. In this review, we will summarize and analyze the accumulated data concerning long non-coding RNAs (lncRNAs) that are transcribed from sense (coding) DNA strands of Hox clusters. It was shown that antisense regulatory RNAs control the work of Hox genes in cis and trans, participate in the establishment and maintenance of the epigenetic code of Hox loci, and can even serve as a source of regulatory peptides that switch cellular energetic metabolism. Moreover, these molecules can be considered as a force that consolidates the cluster into a single whole. We will discuss the examples of antisense transcription of Hox genes in well-studied systems (cell cultures, morphogenesis of vertebrates) and bear upon some interesting examples of antisense Hox RNAs in non-model Protostomia.