Hox genes in neural patterning and circuit formation in the mouse hindbrain.

The mammalian hindbrain is the seat of regulation of several vital functions that involve many of the organ systems of the body. Such functions are controlled through the activity of intricate arrays of neuronal circuits and connections. The establishment of ordered patterns of neuronal specification, migration, and axonal topographic connectivity during development is crucial to build such a complex network of circuits and functional connectivity in the mature hindbrain. The early development of the vertebrate hindbrain proceeds according to a fundamental metameric partitioning along the anteroposterior axis into cellular compartments known as rhombomeres. Such an organization has been highly conserved in vertebrate evolution and has a fundamental impact on the hindbrain adult structure, nuclear organization, and connectivity. Here, we review the cellular and molecular mechanisms underlying hindbrain neuronal circuitry in the mouse, with a specific focus on the role of the homeodomain transcription factors of the Hox gene family. The Hox genes are crucial determinants of rhombomere segmental identity and anteroposterior patterning. However, recent findings suggest that, in addition to their well-known roles at early embryonic stages, the Hox genes may play important roles also in later aspect of neuronal circuit development, including stereotypic neuronal migration, axon pathfinding, and topographic mapping of connectivity.