Assembly of the Brainstem Cochlear Nuclear Complex Is Revealed by Intersectional and Subtractive Genetic Fate Maps

• DOI: 10.1016/j.neuron.2006.03.014
• Publication Date: 2006-04-20T12:07:09Z
• Authors: Anna F. Farago; Rajeshwar B. Awat...; Susan M. Dymecki
• Keywords: Cochlear Nucleus; Neurons; 0301 basic medicine; Auditory Pathways; Integrases; Neuroscience(all); Gene Expression Profiling; Stem Cells; Gene Expression Regulation, Developmental; DEVBIO; Mice, Transgenic; Immunohistochemistry; MOLNEURO; Mice; 03 medical and health sciences; Cell Movement; DNA Nucleotidyltransferases; Animals; RNA, Messenger; Transgenes; In Situ Hybridization

The cochlear nuclear complex (CN) is the entry point for central auditory processing. Although constituent neurons have been studied physiologically, their embryological origins and molecular profiles remain obscure. Applying intersectional and subtractive genetic fate mapping approaches, we show that this complex develops modularly from genetically separable progenitor populations arrayed as rostrocaudal microdomains within and outside the hindbrain (lower) rhombic lip (LRL). The dorsal CN subdivision, structurally and topographically similar to the cerebellum, arises from microdomains unexpectedly caudal and noncontiguous to cerebellar primordium; ventral CN subdivisions arise from more rostral LRL. Magnocellular regions receive contributions from LRL and coaxial non-lip progenitors; contrastingly, ensheathing granule cells derive principally from LRL. Also LRL-derived and molecularly similar to CN granule cells are precerebellar mossy fiber neurons; surprisingly, these ostensibly intertwined populations have separable origins and adjacent but segregated migratory streams. Together, these findings provide new platforms for investigating the development and evolution of auditory and cerebellar systems.