Fate restriction and developmental potential of cerebellar progenitors. Transplantation studies in the developing CNS

Piercesare Grimaldi, Barbara Carletti, Lorenzo Magrassi, Ferdinando Rossi

Research output: Contribution to journalArticle

Abstract

The generation of cell diversity from undifferentiated progenitors is regulated by interdependent mechanisms, including cell intrinsic programs and environmental cues. This interaction can be investigated by means of heterochronic/heterotopic transplantation, which allows to examine the behaviour of precursor cells in an ususual environment. The cerebellum provides an ideal model to study cell specification, because its neurons originate according to a well-defined timetable and they can be are readily recognised by morphological features and specific markers. Cerebellar progenitors transplated to the embryonic cerebellum develop fully mature cerebellar neurons, which often integrate in the host circuitry in a highly specific manner. In extracerebellar locations, cerebellar progenitors preferentially settle in caudal CNS regions where they exclusively acquire cerebellar identities. By contrast, neocortical precursors preferentially settle in rostral regions and fail to develop hindbrain phenotypes. The phenotypic repertoire generated by transplanted cerebellar progenitors is strictly dependent on their age. Embryonic progenitors originate all mature cerebellar cells, whereas postnatal ones exclusively generate later-born types, such as molecular layer interneurons and granule cells. Together, these observations foster the hypothesis that neural progenitors are first specified towards region-specific phenotypes along the rostro-caudal axis of the neural tube. Thereafter, the developmental potential of progenitor cells is progressively restricted towrds later generated types. Such a progressive specification of precursor cells in space and time is stably transmitted to their progeny and it cannot be modified by local cues, when these cells are confronted with heterotopic and/or heterochronic environments.

Original languageEnglish
Pages (from-to)57-68
Number of pages12
JournalProgress in Brain Research
Volume148
DOIs
Publication statusPublished - 2004

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Keywords

  • cell specification
  • cerebellar development
  • commitment
  • differentiation
  • EGL external granular layer
  • in utero transplantation
  • neural graft
  • neural progenitor

ASJC Scopus subject areas

  • Neuroscience(all)

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