Time constraints and positional cues in the developing cerebellum regulate Purkinje cell placement in the cortical architecture

Barbara Carletti, Ian Martin Williams, Ketty Leto, Kazunori Nakajima, Lorenzo Magrassi, Ferdinando Rossi

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

To elucidate the mechanisms that regulate neuronal placement and integration in the cerebellar circuitry, we assessed the fate of Purkinje cells transplanted to embryonic, juvenile and adult hosts, asking how architectural changes of the developing cortex influence their anatomical incorporation. Donor Purkinje cells navigate through the host parenchyma either along their natural migratory pathway or following unusual routes. In the latter case, donor neurons fail to orientate correctly and to establish the cortico-nuclear projection. Purkinje cells that follow the physiological route achieve the typical orientation and connectivity, but end displaced in the molecular layer if their arrival in the recipient cortex is delayed. Navigation routes and final settling of donor neurons vary with host age, depending on the ontogenetic construction of cortical layering, and particularly on the maturation of granule cells. The migratory behavior and homing of transplanted Purkinje cells is modified after external granular layer ablation, or neutralization of reelin signaling produced by granule cells. Therefore, although the cerebellar milieu remains receptive for Purkinje cells even after the end of development, correct placement of donor neurons depends on the timing of their migration, related to cerebellar developmental dynamics and granule cell layering.

Original languageEnglish
Pages (from-to)147-160
Number of pages14
JournalDevelopmental Biology
Volume317
Issue number1
DOIs
Publication statusPublished - 2008 May 1

Keywords

  • Cell replacement
  • Granule cell
  • Neural progenitors
  • Neural transplantation
  • Neuronal differentiation
  • Neuronal migration
  • Purkinje cell
  • Reelin

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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