A Hox gene regulatory network for hindbrain segmentation

Abstract

In vertebrates, the hindbrain serves as a highly conserved complex coordination center for regulating many fundamental activities of the central nervous system, such as respiratory rhythms, sleep patterns and equilibrium, and it also plays an important role in craniofacial development. The basic ground plan that underlies the diverse functions of the hindbrain and its neural crest derivatives is established and patterned by a process of segmentation. Through a dynamic series of signaling and regulatory interactions the developing hindbrain is transiently compartmentalized into a set of seven segmental units, termed rhombomeres. The nested expression of the Hox family of transcription factors is tightly coupled to the process of segmentation and provides a molecular code for specifying the unique regional properties of the hindbrain and its neural crest derived craniofacial structures. The high degree of similarity in hindbrain architecture between diverse vertebrates has enabled cross-species regulatory analysis. This has facilitated the experimental assembly of the signaling and regulatory interactions, which underlie the process of segmentation, into a Hox-dependent gene regulatory network (GRN) model. This hindbrain GRN is a key regulatory feature of head patterning, conserved to the base of vertebrate evolution. This regulatory framework also serves as a basis for comparing and contrasting GRNs that govern cranial neural crest formation and axial patterning and provide insight into regulatory mechanisms associated with the evolution of novel vertebrate traits. The purpose of this review is to discuss the majorfeatures of the GRN for hindbrain segmentation and its relationship to the broader functional role of the hindbrain in patterning head development.

Keywords: Hindbrain; Hox expression; Hox genes; Hox phenotypes; Neural crest; Segmentation; Vertebrate evolution.