Life Science

Segmental Arithmetic: Summing Up the Hox Gene Regulatory Network for Hindbrain Development in Chordates

It is important to understand when and how the hindbrain segmentation program evolved. Recent studies have shed some light.

The hindbrain is a complex and essential coordination center of the vertebrate brain. It receives sensory information such as the perception of taste, touch, hearing and balance, whilst transmitting motor impulses to the head muscles. A network of hindbrain neurons relay with other parts of the brain to coordinate complex motor functions, including locomotion, postural control, breathing and vocalisation.

During embryonic development, the hindbrain consists of a series of segmental bulges (rhombomeres) along the head-to-tail axis. Experimental data from a variety of vertebrate model organisms reveal that this early segmentation is crucial for setting up the later neuronal architecture of the hindbrain as well as for the proper development of the head and neck. Studies over the last 25 years have provided important insights into the molecular cascades that generate hindbrain segments and specify their outcomes in vertebrates. This wealth of knowledge can be represented as a gene regulatory network that provides a framework to interpret experimental data, generate hypotheses and identify gaps in our understanding of the progressive processes of hindbrain segmentation.

The Hox family of transcription factors are encoded by genes  that reside in genomic clusters and play key roles at multiple stages in this network. Hox genes exhibit segmental domains of activity in the hindbrain that are remarkably similar between different vertebrate species. In contrast to vertebrates, invertebrate species have relatively simple brains and lack hindbrain segments. It is widely held that the emergence of hindbrain segmentation and its integration with head patterning are fundamentally important events during the evolution of the complex vertebrate head. Thus, it is important to understand when and how the hindbrain segmentation program evolved.

Recent studies investigating Hox genes in the jawless vertebrate sea lamprey and in invertebrate species have shed light on this problem. These approaches reveal that the gene regulatory network for hindbrain segmentation was a feature of ancestral vertebrates and they suggest that it evolved in a series of steps through elaboration of an ancient head-to-tail patterning network.

View the full article on WIREs Developmental Biology

Kindly contributed by Hugo Parker.

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