Organization of the human embryonic ventral mesencephalon

The neurons in the ventral mesencephalon (VM) are organized into several nuclei consisting of distinct neuronal populations. These include the dopaminergic (DA) neurons of the substania nigra and ventral tegmental area, the oculomotor (OM) neurons that innervate the muscles controlling eye movement, and the reticular neurons of the red nucleus (RN) involved in motor control and coordination reviewed in Puelles (2007). The factors and genes that control the differentiation of the various neuronal populations in the VM have been extensively studied in the mouse and other model organisms but little is known about the progenitors and their protein expression in the developing human brain. In this study we analyze if key regulators identified in rodents are also expressed in the human VM during embryonic development. We report that BLBP and LMX1A mark the floor plate and that FOXA2 is expressed in both the floor plate and basal plate of the human VM. The proneural transcription factors NGN2 and MASH1 are expressed in the ventricular zone of the human VM within and lateral to the floor plate. The post-mitotic DA neurons express TH as well as NURR1 and PITX3. ISL1 and BRN3A can be used to detect the cells of OM and RN, respectively. We show that many key developmental control factors are expressed in a temporal and spatial manner in the human VM essentially corresponding to what has been observed in the mouse. This data therefore suggest similar roles for these factors also in human VM development and dopamine neurogenesis.