Origin of climbing fiber neurons and the definition of rhombic lip.

Wilhelm His identified the rhombic lip in human embryos a century ago and thought that all mossy and climbing fiber neurons are derived from it. This has been accepted for more than one hundred years. However, recent genetic fate mapping studies have demonstrated that mossy fiber and climbing fiber neurons have distinct progenitor pools and originate from different subdomains in the ventricular zone of the caudal hindbrain. The majority of climbing fiber neurons has been found to derive from more medial parts of the caudal hindbrain although its dorsal boundary is unclear currently. Subsequently, several new definitions for the rhombic lip have been made according to the expression domain of different transcription factors, such as Math1, Wnt1 and Olig3, which have different ventral boundaries and make the area of rhombic lip confused. Therefore, a precise definition for rhombic lip is still lacking for the main reason that the origin of the entire inferior olivary nuclei is still unclear. Further genetic fate mapping is needed to determine the origin of all climbing fiber neurons which will help to give the rhombic lip an unambiguous definition. Crown