A key role for the HLH transcription factor EBF2COE2,O/E-3 in Purkinje neuron migration and cerebellar cortical topography

被引:76
作者
Croci, Laura
Chung, Seung-Hyuk
Masserdotti, Giacomo
Gianola, Sara
Bizzoca, Antonella
Gennarini, Gianfranco
Corradi, Anna
Rossi, Ferdinando
Hawkes, Richard
Consalez, G. Giacomo
机构
[1] San Raffaele Sci Inst, I-20132 Milan, Italy
[2] Univ Calgary, Dept Cell Biol & Anat, Genes & Dev Res Grp, Calgary, AB T2N 4N1, Canada
[3] Univ Calgary, Hotchkiss Brain Inst, Fac Med, Calgary, AB T2N 4N1, Canada
[4] Univ Turin, Rita Levi Montalcini Ctr Brain Repair, Dept Neurosci, Physiol Sect, Turin, Italy
[5] Univ Bari, Sch Med, Dept Pharmacol & Human Physiol, Bari, Italy
来源
DEVELOPMENT | 2006年 / 133卷 / 14期
关键词
cerebellum; Purkinje neurons; neuronal migration; transcription factor; parasagittal stripes; Zebrin II; cerebellar map; Olf-1; early B-cell factor;
D O I
10.1242/dev.02437
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:2719 / 2729
页数:11
相关论文
共 73 条
[1]  
AHN AH, 1994, DEVELOPMENT, V120, P2081
[2]   Selective purkinje cell ectopia in the cerebellum of the weaver mouse [J].
Armstrong, C ;
Hawkes, R .
JOURNAL OF COMPARATIVE NEUROLOGY, 2001, 439 (02) :151-161
[3]  
Armstrong CL, 2000, J COMP NEUROL, V416, P383, DOI 10.1002/(SICI)1096-9861(20000117)416:3<383::AID-CNE9>3.0.CO
[4]  
2-M
[5]  
Armstrong CL, 2001, J COMP NEUROL, V429, P7, DOI 10.1002/1096-9861(20000101)429:1<7::AID-CNE2>3.0.CO
[6]  
2-Q
[7]   Constitutive expression of heat shock protein HSP25 in the central nervous system of the developing and adult mouse [J].
Armstrong, CL ;
Krueger-Naug, AM ;
Currie, RW ;
Hawkes, R .
JOURNAL OF COMPARATIVE NEUROLOGY, 2001, 434 (03) :262-274
[8]   Pattern formation in the cerebellar cortex [J].
Armstrong, CL ;
Hawkes, R .
BIOCHEMISTRY AND CELL BIOLOGY, 2000, 78 (05) :551-562
[9]  
Beierbach E, 2001, J COMP NEUROL, V436, P42
[10]   ZEBRIN-II - A POLYPEPTIDE ANTIGEN EXPRESSED SELECTIVELY BY PURKINJE-CELLS REVEALS COMPARTMENTS IN RAT AND FISH CEREBELLUM [J].
BROCHU, G ;
MALER, L ;
HAWKES, R .
JOURNAL OF COMPARATIVE NEUROLOGY, 1990, 291 (04) :538-552