Transcription factors in the development of medial hypothalamic structures

The hypothalamus has historically been subdivided into nuclei, agglomerations of cell bodies that are visually distinct in histological sections. Regulatory functions of metabolism have been assigned to the various hypothalamic nuclei principally by analysis of animals with lesions of individual nuclei (39) but also via various means of stimulation, such as cooling or heating probes. Biochemical and molecular specificity of these studies became possible with the identification and synthesis of neurotransmitters (7, 38) as well as the means to manipulate the expression of endogenous neurotransmitters (35, 37) and their receptors by genetic means (6, 21). The arcuate nucleus (ARC) is likely to be the primary site for neurons that sense circulating fuels and energy reserves (POMC/CART neurons, NPY/AGRP neurons), whereas the paraventricular nucleus (PVN) receives input from the ARC and harbors many of the releasing factors (CRF, TRH, vasopressin, and oxytocin) that control pituitary hormone release. The ventromedial nucleus (VMN) receives input from the ARC and plays a critical role in energy balance in parallel with the ARC. The VMN and PVN also send descending projections to the autonomic nervous system and other pathways that control ingestive behavior and metabolism. Developmental analyses have revealed that the neurons that comprise the hypothalamic nuclei arise by differentiation and migration from stem cells within the ventricular zone. Based on recent work, it is becoming clear that coordination between numerous transcription factors that determine specification, survival, and migration is necessary for the formation of the hypothalamus, with each nucleus being determined by its own unique set of factors. In this minireview, we will provide a selective view of the roles that transcription factors play in the developing hypothalamus.