QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online 14 June 2006
doi: 10.1242/dev.02437

This Article Figures Only Full Text Full Text (PDF) Supplementary Material All Versions of this Article: dev.02437v1 133/14/2719    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Croci, L. Articles by Consalez, G. G. Search for Related Content PubMed PubMed Citation Articles by Croci, L. Articles by Consalez, G. G.

A key role for the HLH transcription factor EBF2^COE2,O/E-3 in Purkinje neuron migration and cerebellar cortical topography

Laura Croci¹, Seung-Hyuk Chung², Giacomo Masserdotti¹, Sara Gianola³, Antonella Bizzoca⁴, Gianfranco Gennarini⁴, Anna Corradi^1,*, Ferdinando Rossi³, Richard Hawkes² and G. Giacomo Consalez^1,

¹ San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milan, Italy.
² Department of Cell Biology and Anatomy, Genes and Development Research Group, and Hotchkiss Brain Institute, Faculty of Medicine, University of Calgary, Calgary, Alberta T2N 4N1, Canada.
³ Rita Levi Montalcini Center for Brain Repair, Department of Neuroscience, Section of Physiology, University of Turin, Italy.
⁴ Department of Pharmacology and Human Physiology, University of Bari School of Medicine, Italy.

Author for correspondence (e-mail: g.consalez{at}hsr.it)

Accepted 9 May 2006

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.

Key words: Cerebellum, Purkinje neurons, Neuronal migration, Transcription factor, Parasagittal stripes, Zebrin II, Cerebellar map, Olf-1, Early B-cell factor

This article has been cited by other articles:

				R. V. Sillitoe, D. Stephen, Z. Lao, and A. L. Joyner Engrailed Homeobox Genes Determine the Organization of Purkinje Cell Sagittal Stripe Gene Expression in the Adult Cerebellum J. Neurosci., November 19, 2008; 28(47): 12150 - 12162. [Abstract] [Full Text] [PDF]

				A-r. Jung, T. W. Kim, I. J. Rhyu, H. Kim, Y. D. Lee, S. Vinsant, R. W. Oppenheim, and W. Sun Misplacement of Purkinje Cells during Postnatal Development in Bax Knock-Out Mice: A Novel Role for Programmed Cell Death in the Nervous System? J. Neurosci., March 12, 2008; 28(11): 2941 - 2948. [Abstract] [Full Text] [PDF]

				W. A. Alcaraz, D. A. Gold, E. Raponi, P. M. Gent, D. Concepcion, and B. A. Hamilton Zfp423 controls proliferation and differentiation of neural precursors in cerebellar vermis formation PNAS, December 19, 2006; 103(51): 19424 - 19429. [Abstract] [Full Text] [PDF]