Abstract
The molecular mechanisms that regulate the production and diversity of olfactory bulb interneurons remain poorly understood. With the exception of the GABAergic/dopaminergic subtype in the glomerular layer, no information exists concerning the generation of the other subtypes. Here we show that the recently identified zinc finger transcription factor Sp8 is expressed in neurogenic regions, which give rise to olfactory bulb interneurons at embryonic and postnatal time points and remains expressed in the calretinin-expressing and GABAergic/nondopaminergic interneurons of the glomerular layer. Conditional inactivation of Sp8 in the embryonic ventral telencephalon reveals a requirement for the normal generation of these interneuron subtypes. Sp8 conditional mutants exhibit an increase in cell death within the lateral ganglionic eminence and rostral migratory stream. Moreover, mutant neuroblasts/interneurons are misspecified and display abnormal migration patterns in the olfactory bulb, indicating that Sp8 contributes to olfactory bulb interneuron diversity by regulating the survival, migration, and molecular specification of neuroblasts/interneurons.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Animals, Newborn
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Bromodeoxyuridine / metabolism
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Calbindin 2
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Calbindins
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Cell Count / methods
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Cell Death / genetics
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Cell Differentiation / physiology
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Cell Movement / physiology
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DNA-Binding Proteins / deficiency
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DNA-Binding Proteins / physiology*
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Embryo, Mammalian
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Fluorescent Antibody Technique / methods
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Gene Expression Regulation, Developmental / physiology*
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Glutamate Decarboxylase / metabolism
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Green Fluorescent Proteins / metabolism
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Homeodomain Proteins / genetics
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Homeodomain Proteins / physiology
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In Situ Hybridization / methods
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In Situ Nick-End Labeling
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Interneurons / classification
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Interneurons / physiology*
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Isoenzymes / metabolism
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Mice
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Mice, Knockout
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Models, Biological
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Olfactory Bulb* / cytology
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Olfactory Bulb* / embryology
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Olfactory Bulb* / growth & development
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PAX2 Transcription Factor / genetics
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S100 Calcium Binding Protein G / metabolism
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Transcription Factors / deficiency
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Transcription Factors / physiology*
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Tyrosine 3-Monooxygenase / metabolism
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gamma-Aminobutyric Acid / metabolism
Substances
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Calb2 protein, mouse
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Calbindin 2
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Calbindins
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DNA-Binding Proteins
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Gsh2 protein, mouse
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Homeodomain Proteins
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Isoenzymes
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PAX2 Transcription Factor
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Pax2 protein, mouse
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S100 Calcium Binding Protein G
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Sp8 protein, mouse
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Transcription Factors
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Green Fluorescent Proteins
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gamma-Aminobutyric Acid
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Tyrosine 3-Monooxygenase
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Glutamate Decarboxylase
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glutamate decarboxylase 2
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Bromodeoxyuridine