title: Early subdivisions in the neural plate define distinct competence for inductive signals.
abstract: Regionalization of the embryonic brain is achieved through multi-step processes that operate sequentially and/or simultaneously. Localized sources of various signaling molecules act as organizing centers that pattern neighboring fields to create molecularly distinct domains. We investigated the mechanisms underlying the regionally distinct competence for two such organizing signals, Fibroblast growth factor 8 (Fgf8) and Sonic hedgehog (Shh), using chick embryos. First, we demonstrated that FGF receptor 1 (Fgfr1) and Fgfr3, expressed differentially in the developing brain, possess an equivalent potential to induce the regionally distinct Fgf8-responsive genes, depending on the anterior-posterior dimension of the brain. Next we found that homeodomain transcription factors Six3 and Irx3 can alter the regional responses to both Fgf8 and Shh in the forebrain. Six3 confers the ability to express Bf1, a gene essential for the telencephalon and eye development, and Nkx2.1, which is required for development of the hypothalamus. In contrast, Irx3 confers the ability to express En2 and Nkx6.1 in response to Fgf8 and Shh, respectively. Furthermore, an alteration in the region-specific response to Fgf8 upon misexpression of Irx3 resulted in transformation of diencephalic and possibly telencephalic tissues into the optic tectum. Finally, we demonstrated that Six3 and Irx3 can mutually repress their expression, which may contribute to the establishment of their complementary expression domains in the neural plate. These repressive interactions are specific, as Six3 did not repress Gbx2, and Irx3 did not disturb Otx2 expression. These findings provide evidence that the early embryonic forebrain is demarcated into two domains with distinct genetic programs, which argues against the authentic telendiencephalic subdivision.
authors.affiliation: Department of Neurobiology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kobayashi
authors.forename: Makoto
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Ken
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Ogura
authors.forename: Masato
authors.initials: M
authors.lastname: Nakafuku
authors.forename: Kenji
authors.initials: K
authors.lastname: Shimamura
mesh_terms: D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000196:embryology* / Q000502:physiology; D002642:Chick Embryo; D004625:Embryo, Nonmammalian / Q000196:embryology / Q000502:physiology; D004627:Embryonic Induction / Q000502:physiology*; D005136:Eye Proteins; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors / Q000502:physiology*; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000502:physiology; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051498:Receptor, Fibroblast Growth Factor, Type 3; D017468:Receptors, Fibroblast Growth Factor / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology; D000097607:Homeobox Protein SIX3
chemical_list: D005136:Eye Proteins; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051498:Receptor, Fibroblast Growth Factor, Type 3; D017468:Receptors, Fibroblast Growth Factor; D015534:Trans-Activators; D014157:Transcription Factors; D000097607:Homeobox Protein SIX3