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First published online November 10, 2005
doi: 10.1242/10.1242/dev.02094

Development 132, 5185-5197 (2005)
Published by The Company of Biologists 2005
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Directed differentiation of neural cells to hypothalamic dopaminergic neurons

Kyoji Ohyama1,*, Pamela Ellis1, Shioko Kimura2 and Marysia Placzek1,*

1 Department of Biomedical Science, University of Sheffield, Firth Court, Western Bank, Sheffield S10 2TN, UK
2 National Cancer Institute, National Institute of Health, MD, 20892, USA

* Authors for correspondence (e-mail: k.ohyama{at}sheffield.ac.uk and m.placzek{at}sheffield.ac.uk)

Accepted 19 September 2005

Hypothalamic neurons play a key role in homeostasis, yet little is known about their differentiation. Here, we demonstrate that Shh and Bmp7 from the adjacent prechordal mesoderm govern hypothalamic neural fate, their sequential action controlling hypothalamic dopaminergic neuron generation in a Six3-dependent manner. Our data suggest a temporal distinction in the requirement for the two signals. Shh acts early to specify dopaminergic neurotransmitter phenotype. Subsequently, Bmp7 acts on cells that are ventralised by Shh, establishing aspects of hypothalamic regional identity in late-differentiating/postmitotic cells. The concerted actions of Shh and Bmp7 can direct mouse embryonic stem cell-derived neural progenitor cells to a hypothalamic dopaminergic fate ex vivo.

Key words: Shh, Bmp7, Chick, Dopamine, Hypothalamus


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