title: Otx dose-dependent integrated control of antero-posterior and dorso-ventral patterning of midbrain.
abstract: Organizing centers emit signaling molecules that specify different neuronal cell types at precise positions along the anterior-posterior (A-P) and dorsal-ventral (D-V) axes of neural tube during development. Here we report that reduction in Otx proteins near the alar-basal plate boundary (ABB) of murine midbrain resulted in a dorsal shift of Shh expression, and reduction in Otx proteins at the midbrain-hindbrain boundary (MHB) resulted in an anterior expansion of the Fgf8 domain. Our data thus indicate that an Otx dose-dependent repressive effect coordinates proper positioning of Shh and Fgf8 expression. Furthermore, this control is effective for conferring proper cell identity in the floor-plate region of midbrain and does not require an Otx2-specific property. We propose that this mechanism may provide both A-P and D-V positional information to neuronal precursors located within the midbrain.
authors.affiliation: MRC Centre for Developmental Neurobiology, New Hunt's House, 4th Floor, King's College London, Guy's Campus, London Bridge, London SE1 1UL, UK.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Puelles
authors.forename: Dario
authors.initials: D
authors.lastname: Acampora
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Lacroix
authors.forename: Massimo
authors.initials: M
authors.lastname: Signore
authors.forename: Alessandro
authors.initials: A
authors.lastname: Annino
authors.forename: Francesca
authors.initials: F
authors.lastname: Tuorto
authors.forename: Stefania
authors.initials: S
authors.lastname: Filosa
authors.forename: Giorgio
authors.initials: G
authors.lastname: Corte
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wurst
authors.forename: Siew-Lan
authors.initials: SL
authors.lastname: Ang
authors.forename: Antonio
authors.initials: A
authors.lastname: Simeone
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D008636:Mesencephalon / Q000196:embryology* / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D051857:Otx Transcription Factors; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics; D015534:Trans-Activators / Q000096:biosynthesis* / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D051857:Otx Transcription Factors; C497660:Otx2 protein, mouse; D011994:Recombinant Proteins; D015534:Trans-Activators; D014157:Transcription Factors