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The Journal of Neuroscience, November 1, 2001, 21(21):8505-8513

Phenotypic Differentiation during Migration of Dopaminergic Progenitor Cells to the Olfactory Bulb

Harriet Baker, Nian Liu, Hong S. Chun, Sachiko Saino, RoseAnn Berlin, Bruce Volpe, and Jin H. Son

Burke Medical Research Institute, Weill Medical College, Cornell University, White Plains, New York 10605

A possible source for transplantable neurons in Parkinson's disease are adult olfactory bulb (OB) dopamine (DA) progenitors that originate in the anterior subventricular zone and reach the OB through the rostral migratory stream. We used adult transgenic mice expressing a lacZ reporter directed by an 8.9 kb tyrosine hydroxylase (TH) promoter to investigate the course of DAergic differentiation. Parallel transgene and intrinsic TH mRNA expression occurred during migration of DA interneurons through the mitral and superficial granule cell layers before these cells reached their final periglomerular position. Differential transgene and calcium-calmodulin-dependent protein kinase IV expression distinguished two nonoverlapping populations of interneurons. Transgenic mice carrying a TH8.9kb/lacZ construct with a mutant AP-1 site demonstrated that this element confers OB DA-specific TH gene regulation. These results indicate that DA phenotypic determination is specific to a subset of mobile OB progenitors.

Key words: tyrosine hydroxylase; Parkinson's disease; stem cell; migration; rostral migratory stream; subventricular zone; dopamine

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Copyright © 2001 Society for Neuroscience  0270-6474/01/21218505-09$05.00/0

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