Postnatal development of the murine cerebellar cortex: formation and early dispersal of basket, stellate and Golgi neurons.
The cerebellar cortex consists of a small set of neuronal cell types interconnected in a highly stereotyped way. While the development of cerebellar cortical projection neurons, i.e. Purkinje cells, and that of granule cells has been elucidated in considerable detail, that of cerebellar cortical inhibitory interneurons is still rather fragmentarily understood. Here, we use mice expressing green fluorescent protein (GFP) from the Pax2 locus to analyse the ontogenesis of these cells. Numbers of Pax2-positive inhibitory interneuronal precursors increase following a classical sigmoidal growth curve to yield a total of some 905.000 +/- 77.000 cells. Maximal cell increase occurs at about postnatal day (P)5.4, and some 75% of all inhibitory interneurons are generated prior to P7. Conjoint analysis of the developmental accruement of Pax2-GFP-positive cells and their cell cycle distribution reveals that, at least at P0 and P3, the numerical increase of these cells results primarily from proliferation of a Pax2-negative precursor population and suggests that Pax2 expression begins at or around the final mitosis. Following their terminal mitosis, inhibitory cerebellar cortical interneurons go through a protracted quiescent phase in which they maintain expression of the cell cycle marker Ki-67. During this phase, they translocate into the nascent molecular layer, where they stall next to premigratory granule cell precursors without penetrating this population of cells. These observations provide a quantitative description of cerebellar cortical inhibitory interneuron genesis and early differentiation, and define Pax2 as a marker expressed in basket and stellate cells, from around their final mitosis to their incipient histogenetic integration.
Weisheit
Gunnar
G
Anatomisches Institut, Anatomie and Zellbiologie, University of Bonn, Bonn, Germany.
Gliem
Michael
M
Endl
Elmar
E
Pfeffer
Peter L
PL
Busslinger
Meinrad
M
Schilling
Karl
K
D000375:Aging / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation; D002525:Cerebellar Cortex / Q000166:cytology / Q000254:growth & development*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007395:Interneurons / Q000166:cytology / Q000378:metabolism*; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009433:Neural Inhibition / Q000502:physiology; D009434:Neural Pathways / Q000166:cytology / Q000254:growth & development; D051762:PAX2 Transcription Factor / Q000235:genetics / Q000378:metabolism*
D015415:Biomarkers; D019394:Ki-67 Antigen; C498355:Mki67 protein, mouse; D051762:PAX2 Transcription Factor; C497319:Pax2 protein, mouse; D049452:Green Fluorescent Proteins