Migration, early axonogenesis, and Reelin-dependent layer-forming behavior of early/posterior-born Purkinje cells in the developing mouse lateral cerebellum.
BACKGROUND
Cerebellar corticogenesis begins with the assembly of Purkinje cells into the Purkinje plate (PP) by embryonic day 14.5 (E14.5) in mice. Although the dependence of PP formation on the secreted protein Reelin is well known and a prevailing model suggests that Purkinje cells migrate along the 'radial glial' fibers connecting the ventricular and pial surfaces, it is not clear how Purkinje cells behave in response to Reelin to initiate the PP. Furthermore, it is not known what nascent Purkinje cells look like in vivo. When and how Purkinje cells start axonogenesis must also be elucidated.


RESULTS
We show that Purkinje cells generated on E10.5 in the posterior periventricular region of the lateral cerebellum migrate tangentially, after only transiently migrating radially, towards the anterior, exhibiting an elongated morphology consistent with axonogenesis at E12.5. After their somata reach the outer/dorsal region by E13.5, they change 'posture' by E14.5 through remodeling of non-axon (dendrite-like) processes and a switchback-like mode of somal movement towards a superficial Reelin-rich zone, while their axon-like fibers remain relatively deep, which demarcates the somata-packed portion as a plate. In reeler cerebella, the early born posterior lateral Purkinje cells are initially normal during migration with anteriorly extended axon-like fibers until E13.5, but then fail to form the PP due to lack of the posture-change step.


CONCLUSIONS
Previously unknown behaviors are revealed for a subset of Purkinje cells born early in the posteior lateral cerebellum: tangential migration; early axonogenesis; and Reelin-dependent reorientation initiating PP formation. This study provides a solid basis for further elucidation of Reelin's function and the mechanisms underlying the cerebellar corticogenesis, and will contribute to the understanding of how polarization of individual cells drives overall brain morphogenesis.
Miyata
Takaki
T
Department of Anatomy and Cell Biology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan. tmiyata@med.nagoya-u.ac.jp
Ono
Yuichi
Y
Okamoto
Mayumi
M
Masaoka
Makoto
M
Sakakibara
Akira
A
Kawaguchi
Ayano
A
Hashimoto
Mitsuhiro
M
Ogawa
Masaharu
M
D000256:Adenoviridae / Q000502:physiology; D000367:Age Factors; D000818:Animals; D001369:Axons / Q000502:physiology*; D019521:Body Patterning / Q000235:genetics / Q000502:physiology*; D002232:Carbocyanines; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D002531:Cerebellum / Q000166:cytology* / Q000196:embryology*; D004622:Embryo, Mammalian; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics; D018398:Homeodomain Proteins / Q000378:metabolism; D060850:LIM-Homeodomain Proteins; D051379:Mice; D008813:Mice, Inbred ICR; D008818:Mice, Neurologic Mutants; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D055495:Neurogenesis / Q000235:genetics; D009924:Organ Culture Techniques; D011689:Purkinje Cells / Q000166:cytology* / Q000502:physiology; D000091042:Reelin Protein; D012097:Repressor Proteins / Q000378:metabolism; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors
C035005:3,3'-dihexadecylindocarbocyanine; D002232:Carbocyanines; D015816:Cell Adhesion Molecules, Neuronal; C532058:Corl2 protein, mouse; D016326:Extracellular Matrix Proteins; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; C499523:Lhx1 protein, mouse; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; D012097:Repressor Proteins; D014157:Transcription Factors; D049452:Green Fluorescent Proteins; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases
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