Directed differentiation of neural cells to hypothalamic dopaminergic neurons

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 Six...

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Published inDevelopment (Cambridge) Vol. 132; no. 23; pp. 5185 - 5197
Main Authors Ohyama, Kyoji, Ellis, Pamela, Kimura, Shioko, Placzek, Marysia
Format Journal Article
LanguageEnglish
Published England The Company of Biologists Limited 01.12.2005
Subjects
Animals
Bone Morphogenetic Protein 7
Bone Morphogenetic Proteins - physiology
Cell Differentiation
Chick Embryo
Dopamine
Embryo, Mammalian - cytology
Embryonic Induction
Hedgehog Proteins
Hypothalamus - cytology
Hypothalamus - embryology
Mice
Neurons - cytology
Signal Transduction
Stem Cells - cytology
Time Factors
Trans-Activators - physiology
Transforming Growth Factor beta - physiology
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Summary: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.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0950-1991
1477-9129
DOI:10.1242/dev.02094