Regionalization of the Developing Hypothalamus: The Prosomeric and Tripartite Models

The hypothalamus is a conserved structure in the brain of vertebrates that plays key roles in the organism's homeostasis through different functions, including regulation of temperature, sleep, energy balance and reproduction. The hypothalamus is composed of juxtaposed nuclei, showing dense organization. During development, anterior, tuberal and posterior subdivisions are observed. However, because of the complexity of its organization, the development of hypothalamic architecture is the subject of different developmental models. First, the prosomeric model argues that the hypothalamus is an anterior structure, divided into two distinct hypothalamic prosomeres, and proposes subdivisions within them based on gene expression patterns. Second, the recently established tripartite model based on gene expression patterns, scRNAseq, fate mapping, and functional assays proposes that the hypothalamus is largely a diencephalic structure, organized in areas/nuclei, and the retromammillary area is a posterior hypothalamic boundary within the diencephalon, ventral to the ZLI. In addition to the prosomeric and tripartite models, key molecular processes that underlie the formation of hypothalamic areas are discussed. Finally, this work argues for the tripartite model as the key model of hypothalamic formation in vertebrate species.