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First published online 17 September 2008
doi: 10.1242/dev.024232

Development 135, 3401-3413 (2008)
Published by The Company of Biologists 2008
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Dopaminergic neuronal cluster size is determined during early forebrain patterning

Niva Russek-Blum1, Amos Gutnick1, Helit Nabel-Rosen1, Janna Blechman1, Nicole Staudt2, Richard I. Dorsky3, Corinne Houart2 and Gil Levkowitz1,*

1 Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
2 Medical Research Council Centre for Developmental Neurobiology, King's College, London SE1 1UL, UK.
3 Department of Neurobiology and Anatomy, University of Utah, Salt Lake City, UT 84132, USA.

* Author for correspondence (e-mail: gil.levkowitz{at}weizmann.ac.il)

Accepted 26 August 2008

We have explored the effects of robust neural plate patterning signals, such as canonical Wnt, on the differentiation and configuration of neuronal subtypes in the zebrafish diencephalon at single-cell resolution. Surprisingly, perturbation of Wnt signaling did not have an overall effect on the specification of diencephalic fates, but selectively affected the number of dopaminergic (DA) neurons. We identified the DA progenitor zone in the diencephalic anlage of the neural plate using a two-photon-based uncaging method and showed that the number of non-DA neurons derived from this progenitor zone is not altered by Wnt attenuation. Using birthdating analysis, we determined the timing of the last cell division of DA progenitors and revealed that the change in DA cell number following Wnt inhibition is not due to changes in cell cycle exit kinetics. Conditional inhibition of Wnt and of cell proliferation demonstrated that Wnt restricts the number of DA progenitors during a window of plasticity, which occurs at primary neurogenesis. Finally, we demonstrated that Wnt8b is a modulator of DA cell number that acts through the Fz8a (Fzd8a) receptor and its downstream effector Lef1, and which requires the activity of the Fezl (Fezf2) transcription factor for this process. Our data show that the differential response of distinct neuronal populations to the Wnt signal is not a simple interpretation of their relative anteroposterior position. This study also shows, for the first time, that diencephalic DA population size is modulated inside the neural plate much earlier than expected, concomitant with Wnt-mediated regional patterning events.

Key words: Cell number, Neuronal specification, Oxytocin, Dopamine, Cell lineage






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