title: Generation of thalamic neurons from mouse embryonic stem cells.
abstract: The thalamus is a diencephalic structure that plays crucial roles in relaying and modulating sensory and motor information to the neocortex. The thalamus develops in the dorsal part of the neural tube at the level of the caudal forebrain. However, the molecular mechanisms that are essential for thalamic differentiation are still unknown. Here, we have succeeded in generating thalamic neurons from mouse embryonic stem cells (mESCs) by modifying the default method that induces the most-anterior neural type in self-organizing culture. A low concentration of the caudalizing factor insulin and a MAPK/ERK kinase inhibitor enhanced the expression of the caudal forebrain markers Otx2 and Pax6. BMP7 promoted an increase in thalamic precursors such as Tcf7l2+/Gbx2+and Tcf7l2+/Olig3+cells. mESC thalamic precursors began to express the glutamate transporter vGlut2 and the axon-specific marker VGF, similar to mature projection neurons. The mESC thalamic neurons extended their axons to cortical layers in both organotypic culture and subcortical transplantation. Thus, we have identified the minimum elements sufficient forin vitrogeneration of thalamic neurons. These findings expand our knowledge of thalamic development.
authors.affiliation: Laboratory for Organogenesis and Neurogenesis, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan.|Laboratory of Growth Regulation, Institute for Virus Research, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.|Laboratory for Cell Asymmetry, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Shiraishi
authors.affiliation: Laboratory for Organogenesis and Neurogenesis, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan muguruma@cdb.riken.jp.|Laboratory for Cell Asymmetry, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan.
authors.forename: Keiko
authors.identifier: 0000-0002-3149-4408
authors.initials: K
authors.lastname: Muguruma
authors.affiliation: Laboratory for Organogenesis and Neurogenesis, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Sasai
mesh_terms: D000818:Animals; D055419:Bone Morphogenetic Protein 7 / Q000494:pharmacology; D002449:Cell Aggregation / Q000187:drug effects; D002478:Cells, Cultured; D058732:Embryoid Bodies / Q000166:cytology / Q000187:drug effects; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D016501:Neurites / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D009924:Organ Culture Techniques; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D013788:Thalamus / Q000166:cytology*; D058118:Transcription Factor 7-Like 2 Protein / Q000378:metabolism
chemical_list: D055419:Bone Morphogenetic Protein 7; D009479:Neuropeptides; D047428:Protein Kinase Inhibitors; C544895:Tcf7l2 protein, mouse; D058118:Transcription Factor 7-Like 2 Protein; D020929:Mitogen-Activated Protein Kinase Kinases
keywords: Caudal forebrain; Mouse ES cells; SFEBq; Self-organization; Thalamus