A key role for the HLH transcription factor EBF2COE2,O/E-3 in Purkinje neuron migration and cerebellar cortical topography.
Early B-cell factor 2 (EBF2) is one of four mammalian members of an atypical helix-loop-helix transcription factor family (COE). COE proteins have been implicated in various aspects of nervous and immune system development. We and others have generated and described mice carrying a null mutation of Ebf2, a gene previously characterized in the context of Xenopus laevis primary neurogenesis and neuronal differentiation. In addition to deficits in neuroendocrine and olfactory development, and peripheral nerve maturation, Ebf2 null mice feature an ataxic gait and obvious motor deficits associated with clear-cut abnormalities of cerebellar development. The number of Purkinje cells (PCs) in the Ebf2 null is markedly decreased, resulting in a small cerebellum with notable foliation defects, particularly in the anterior vermis. We show that this stems from the defective migration of a molecularly defined PC subset that subsequently dies by apoptosis. Part of the striped cerebellar topography is disrupted due to cell death and, in addition, many of the surviving PCs, that would normally adopt a zebrin II-negative phenotype, transdifferentiate to Zebrin II-positive, an unprecedented finding suggesting that Ebf2 is required for the establishment of a proper cerebellar cortical map.
Croci
Laura
L
San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milan, Italy.
Chung
Seung-Hyuk
SH
Masserdotti
Giacomo
G
Gianola
Sara
S
Bizzoca
Antonella
A
Gennarini
Gianfranco
G
Corradi
Anna
A
Rossi
Ferdinando
F
Hawkes
Richard
R
Consalez
G Giacomo
GG
D000818:Animals; D017209:Apoptosis; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D002531:Cerebellum / Q000002:abnormalities / Q000166:cytology* / Q000502:physiology; D005260:Female; D007053:Ice; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011689:Purkinje Cells / Q000166:cytology / Q000502:physiology*; D019076:Transgenes; D014982:Xenopus laevis / Q000033:anatomy & histology / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D007053:Ice; C489922:Ebf2 protein, mouse