The neuregulin receptor, ErbB4, is not required for normal development and adult maintenance of the substantia nigra pars compacta.
Degeneration of dopaminergic neurons in the substantia nigra is associated with one of the most prominent human neurological disorders, Parkinson's disease. It is therefore of high interest to identify molecules with trophic effects on this neuronal population. We show here that the neuregulin receptor ErbB4 is differentially expressed in mesencephalic dopaminergic neurons, found in the substantia nigra and in a subregion of the ventral tegmentum but not in the retrorubral field. Early developmental onset and continued expression of ErbB4 into the adult and the presence of two high affinity ligands, neuregulin-1 and betacellulin, in the basal ganglia, suggested that these molecules might participate in the differentiation and/or maintenance of the nigrostriatal system. In order to address this hypothesis, we used a loxP flanked ErbB4 allele in combination with a nestin-Cre transgene and generated brain-specific ErbB4 null mice. These mutant animals survived into adulthood. The distribution of dopaminergic cell bodies in the midbrain, the expression of numerous genes specific to mesencephalic dopaminergic neurons, and the axonal projection to the basal ganglia all appeared normal. Finally, an assessment of their motor function revealed no behavioral deficits. The apparent lack of any mutant phenotype suggests the presence of a strong compensatory mechanism.
Thuret
Sandrine
S
Interdisciplinary Center for Neuroscience, Department of Neuroanatomy, University of Heidelberg, Heidelberg, Germany.
Alavian
Kambiz N
KN
Gassmann
Martin
M
Lloyd
C Kent
CK
Smits
Simone M
SM
Smidt
Marten P
MP
Klein
Rüdiger
R
Dyck
Richard H
RH
Simon
Horst H
HH
D000375:Aging / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001369:Axons / Q000502:physiology; D001921:Brain / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000172:deficiency; D004298:Dopamine / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D066246:ErbB Receptors / Q000502:physiology*; D018398:Homeodomain Proteins; D008024:Ligands; D008636:Mesencephalon / Q000166:cytology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009043:Motor Activity / Q000502:physiology; D009474:Neurons / Q000378:metabolism; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D066247:Receptor, ErbB-4; D017978:Receptors, Growth Factor / Q000378:metabolism; D013378:Substantia Nigra / Q000166:cytology / Q000254:growth & development / Q000502:physiology*; D009435:Synaptic Transmission; D014157:Transcription Factors / Q000172:deficiency; D017557:Ventral Tegmental Area / Q000166:cytology / Q000378:metabolism
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D008024:Ligands; C539882:NR4A2 protein, human; C539883:Nr4a2 protein, mouse; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D017978:Receptors, Growth Factor; D014157:Transcription Factors; C106185:engrailed homeobox proteins; C587689:ERBB4 protein, human; D066246:ErbB Receptors; C587690:Erbb4 protein, mouse; D066247:Receptor, ErbB-4; D004298:Dopamine