Development of the Rhombencephalon: Molecular Evolution and Genetic Regulation

Abstract

The central nervous system develops with incredible precision during embryonic development, controlled by the orchestration of cell fate determination, cell proliferation, and cell growth. The development of the rhombencephalon is the most comprehensively analysed region of the embryonic brain in terms of cell patterning and compartmentalisation. The rhombomeric organisation of the rhombencephalon provides an important cellular and genetic blueprint for establishing many of the characteristic features of the central and peripheral nervous systems. The morphogenesis of the rhombencephalon and the generation of the rhombomeric segments, in an anterior to posterior sequence, coincides with the establishment of precise expression domains of a number of transcription factors (e.g. Hox, kreisler and Krox20), signalling molecules (e.g. Eph/ephrins), membrane and nuclear receptors (such as RAR/RXR) and enzymes involved in the retinoid biosynthetic pathway. In addition, the rhombencephalon is patterned dorsoventrally by key factors such as the BMPs, Fgfs, Wnt and SHH. In this review, the current knowledge of the roles of these signalling factors and the molecular evolutionary evidence for the development of the vertebrate brain in terms of the mechanisms underlying the formation and specification of the rhombencephalon will be discussed.