Journal
NEURON
Volume 49, Issue 4, Pages 503-516Publisher
CELL PRESS
DOI: 10.1016/j.neuron.2006.01.018
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Funding
- NIEHS NIH HHS [ES07051] Funding Source: Medline
- NIMH NIH HHS [MH069643, R01 MH069643-02, R01 MH069643] Funding Source: Medline
- NINDS NIH HHS [R01 NS044080-04, NS044080, R01 NS044080] Funding Source: Medline
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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.
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