Evidence for generative homology of cerebellum and cerebellum-like structures in an elasmobranch fish based on Pax6, Cbln1 and Grid2 expression

J Comp Neurol. 2018 Oct 1;526(14):2187-2203. doi: 10.1002/cne.24473. Epub 2018 Aug 22.

Abstract

The majority of neurons in the mammalian brain reside within the cerebellum (Cb). Yet, the evolutionary origins of the Cb are not well understood. There are several sensory nuclei present across vertebrate phylogeny collectively termed cerebellum-like structures (CbLS) due to a shared anatomy and physiology with the Cb. Despite the similarities, the CbLS are clearly not phylogenetically homologous with the Cb. Common structure and function may arise due to a shared genetic and developmental toolkit. To examine this possibility, we used sequence analysis, western blotting, immunohistochemistry and RT-qPCR to test for the expression of three genes that are critical for mammalian cerebellar development in the Cb and CbLS of an elasmobranch fish, Leucoraja erinacea. In the mammalian Cb, Pax6 is necessary for parallel fiber development, while Cbln1 and Grid2 code for proteins necessary for parallel fiber-principal cell synaptogenesis. Pax6 and Cbln1 are expressed by granule cells in the Cb and CbLS of the adult skate and stage 31 embryo. Grid2 is expressed by principal cells in the Cb and CbLS of the adult and stage 31 embryo. RT-qPCR showed this expression is spatially and temporally restricted to the Cb and CbLS. If Pax6, Cbln1 and Grid2 perform the same functions in the skate Cb and CbLS as they do in the mammalian Cb, then these structures may develop using a shared genetic toolkit and be considered generatively homologous. It is possible that the evolutionary genesis of the Cb was the result of duplication or expansion of the cerebellum-like developmental toolkit.

Keywords: Cbln1; Grid2; Pax6; RRID:AB_10009769; RRID:AB_11020281; RRID:AB_2099233; RRID:AB_2336520; RRID:AB_2336820; RRID:AB_2534017; RRID:AB_791502; RRID:SCR_000667; RRID:SCR_001591; RRID:SCR_002380; RRID:SCR_005302; RRID:SCR_006459; RRID:SCR_014988; cerebellum; cerebellum-like structure; development; evolution.

MeSH terms

  • Animals
  • Base Sequence
  • Cerebellum / anatomy & histology*
  • Cerebellum / embryology
  • Cerebellum / metabolism*
  • Cytoplasmic Granules / metabolism
  • DNA, Complementary / biosynthesis
  • DNA, Complementary / genetics
  • Embryo, Nonmammalian
  • Gene Duplication
  • Gene Expression Regulation
  • Immunohistochemistry
  • Nerve Tissue Proteins / genetics*
  • PAX6 Transcription Factor / genetics*
  • Receptors, Glutamate / genetics*
  • Sequence Homology, Nucleic Acid
  • Skates, Fish / anatomy & histology*

Substances

  • DNA, Complementary
  • Nerve Tissue Proteins
  • PAX6 Transcription Factor
  • Receptors, Glutamate
  • glutamate receptor delta 2
  • cerebellin