The zebrafish cerebellar upper rhombic lip generates tegmental hindbrain nuclei by long-distance migration in an evolutionary conserved manner

J Comp Neurol. 2010 Jul 15;518(14):2794-817. doi: 10.1002/cne.22364.


The upper rhombic lip (URL) of the developing mammalian cerebellum produces different neuronal cell types in a temporal sequence. The first neuronal populations arising from this proliferation zone include the progenitors of the parabrachial, parabigeminal, and laterodorsal-pedunculopontine tegmental hindbrain nuclei. By means of expression analysis, histology, and retrograde neuronal tracing, we have identified the zebrafish homologues of these nuclei, namely, the secondary gustatory/viscerosensory nucleus, the nucleus isthmi, and the superior reticular nucleus, respectively, in the embryonic and larval brain of a stable transgenic wnt1:Gal4-VP16-14 x UAS:GFP zebrafish strain. Combining time-lapse confocal imaging with individual cell tracing, we characterize the migratory behavior of these neuronal precursor populations in detail by revealing their migration path, velocity, and directionality. In addition, we identify neuronal progenitors of the secondary gustatory/viscerosensory nucleus and nucleus isthmi/superior reticular nucleus as belonging to the polysialic acid (PSA)-expressing cell population in the cerebellar plate that migrates in a PSA-dependent manner. Finally, we reveal that circuitries involved in the processing of sensory information (visual, gustatory, general viscerosensory) are already established in the zebrafish larva at day 4 of development. Also the wnt1-expressing pretectal neuronal precursors (not originating from the URL) sending mossy fiber-like projections into the cerebellar corpus are established at that time. In sum, our results show that the origin of neurons of some tegmental hindbrain nuclei, namely, nucleus isthmi/superior reticular nucleus and secondary gustatory/viscerosensory nucleus is in the URL, and that the temporal order of cell types produced by the URL and their developmental program are conserved among vertebrate species.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Axons / physiology
  • Biological Evolution
  • Cell Movement*
  • Cell Proliferation
  • Cerebellum / cytology
  • Cerebellum / embryology
  • Cerebellum / growth & development*
  • Cerebellum / physiology*
  • Immunohistochemistry
  • In Situ Hybridization
  • Larva / growth & development
  • Larva / physiology
  • Neural Pathways / physiology
  • Neuroanatomical Tract-Tracing Techniques
  • Neuronal Tract-Tracers
  • Neurons / physiology*
  • Perception / physiology
  • Rhombencephalon / cytology
  • Rhombencephalon / embryology
  • Rhombencephalon / growth & development*
  • Rhombencephalon / physiology*
  • Stem Cells / physiology
  • Wnt1 Protein / metabolism
  • Zebrafish
  • Zebrafish Proteins / metabolism


  • Neuronal Tract-Tracers
  • Wnt1 Protein
  • Zebrafish Proteins