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First published online September 26, 2008

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Dopaminergic neurogenesis expands with Otx2

Dopaminergic neurons in the ventral midbrain (VM), also known as mesencephalic dopaminergic (mesDA) neurons, control voluntary movements, and their degeneration is associated with Parkinson's disease (PD). In the course of brain development, the establishment of correct VM progenitor domain identity depends on the transcription factor Otx2, but is Otx2 important for mesDA neurogenesis? The answer, as Daniela Omodei and co-workers report on p. 3459, is yes. By analysing mouse mutants that conditionally overexpress Otx2 in the mesencephalon, the authors reveal that too much Otx2 leads to selectively increased mesDA progenitor proliferation and to the expansion of the mesDA progenitor domain. This occurs in a dosage-dependent and anteroposteriorly graded manner. Conversely, lack of Otx2 dramatically reduces mesDA progenitor proliferation and causes early cell cycle exit. The authors also show that Otx2 controls mesDA progenitor proliferation via the canonical Wnt pathway and promotes progenitor differentiation by inducing an intricate transcription factor cascade. These findings flag Otx2 as a potential target for future cell-replacement therapies for PD.

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Related articles in Development:

Anterior-posterior graded response to Otx2 controls proliferation and differentiation of dopaminergic progenitors in the ventral mesencephalon

Daniela Omodei, Dario Acampora, Pietro Mancuso, Nilima Prakash, Luca Giovanni Di Giovannantonio, Wolfgang Wurst, and Antonio Simeone
Development 2008 135: 3459-3470. [Abstract] [Full Text]  

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in Development Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Social Bookmarking                         What's this?