title: Emx2 and Pax6 function in cooperation with Otx2 and Otx1 to develop caudal forebrain primordium that includes future archipallium.
abstract: One of the central issues in developmental neurobiology is how the forebrain is organized ontogenetically. The traditional view is that the anterior neuroectoderm first develops into mesencephalic and prosencephalic vesicles; the latter vesicle subsequently develops into the diencephalon and secondary prosencephalon, of which dorsal parts protrude to generate the telencephalon. The diencephalon yields the pretectum, thalamus, and prethalamus, and the telencephalon produces the archipallium, neopallium, and ganglionic eminences. By identifying cell descendants that once expressed Emx2 with use of the Cre knock-in mutant into the Emx2 locus and analyzing phenotypes of double mutants between Emx2 and Otx2/Otx1 and between Emx2 and Pax6, we propose that at the 3-6 somite stage, the anterior neuroectoderm develops into three primordia: midbrain, caudal forebrain, and rostral forebrain. The caudal forebrain primordium generates not only the pretectum, thalamus, and prethalamus but also the archipallium, cortical hem, choroid plexus, choroidal roof, and eminentia thalami. The primordium corresponds to the Emx2- or Pax6-positive region at the 3-6 somite stage that most probably does not include the future neopallium or commissural plate. Otx2 and Otx1 that are expressed in the entire future forebrain and midbrain cooperate with this Emx2 and Pax6 expression in the development of the caudal forebrain primordium; Emx2 and Pax6 functions are redundant. In the embryonic day 9.5 Emx2-/-Pax6-/- double mutant, the caudal forebrain remained unspecified and subsequently transformed into tectum in a mirror image of the endogenous one.
authors.affiliation: Laboratories for Vertebrate Body Plan, Center for Developmental Biology, RIKEN Kobe, Chuo-ku, Kobe 650-0047, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Kimura
authors.forename: Yoko
authors.initials: Y
authors.lastname: Suda
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kurokawa
authors.forename: Zakir M
authors.initials: ZM
authors.lastname: Hossain
authors.forename: Miwa
authors.initials: M
authors.lastname: Nakamura
authors.forename: Maiko
authors.initials: M
authors.lastname: Takahashi
authors.forename: Akemi
authors.initials: A
authors.lastname: Hara
authors.forename: Shinichi
authors.initials: S
authors.lastname: Aizawa
mesh_terms: D000818:Animals; D000941:Antigens / Q000235:genetics / Q000378:metabolism; D004622:Embryo, Mammalian; D047108:Embryonic Development / Q000235:genetics; D036383:Ephrin-A2 / Q000235:genetics / Q000378:metabolism; D051524:Fibroblast Growth Factor 8 / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D005838:Genotype; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017403:In Situ Hybridization / Q000379:methods; D019426:Integrases; D051379:Mice; D008817:Mice, Mutant Strains; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D051857:Otx Transcription Factors / Q000235:genetics / Q000502:physiology*; D016548:Prosencephalon / Q000033:anatomy & histology / Q000196:embryology* / Q000378:metabolism*; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism; D036225:Receptor, EphB1 / Q000235:genetics / Q000378:metabolism; D017457:Receptors, Albumin / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism; D001616:beta-Galactosidase / Q000378:metabolism; D000099216:Chondroitin Sulfate Proteoglycan 4; D000099260:Empty Spiracles Homeobox Proteins
chemical_list: D000941:Antigens; D036383:Ephrin-A2; D051524:Fibroblast Growth Factor 8; D018398:Homeodomain Proteins; D019426:Integrases; D009419:Nerve Tissue Proteins; D051857:Otx Transcription Factors; D011509:Proteoglycans; D036225:Receptor, EphB1; D017457:Receptors, Albumin; D014157:Transcription Factors; D051153:Wnt Proteins; D001616:beta-Galactosidase; D000099216:Chondroitin Sulfate Proteoglycan 4; D000099260:Empty Spiracles Homeobox Proteins; C496457:Fgf8 protein, mouse; C497656:Otx1 protein, mouse; C497660:Otx2 protein, mouse; C091986:transthyretin receptor; C045073:Cre recombinase