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 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.
Ohyama
Kyoji
K
Department of Biomedical Science, University of Sheffield, Firth Court, Western Bank, Sheffield S10 2TN, UK. k.ohyama@sheffield.ac.uk
Ellis
Pamela
P
Kimura
Shioko
S
Placzek
Marysia
M
D000818:Animals; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000502:physiology; D002454:Cell Differentiation; D002642:Chick Embryo; D004298:Dopamine; D004622:Embryo, Mammalian / Q000166:cytology; D004627:Embryonic Induction; D053823:Hedgehog Proteins; D007031:Hypothalamus / Q000166:cytology* / Q000196:embryology; D051379:Mice; D009474:Neurons / Q000166:cytology*; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology; D013997:Time Factors; D015534:Trans-Activators / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000502:physiology
D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D053823:Hedgehog Proteins; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D004298:Dopamine