Martinez-Barbera, Juan Pedro;
Signore, Massimo;
Boyl, Pietro Pilo;
Puelles, Eduardo;
Acampora, Dario;
Gogoi, Robin;
Schubert, Frank;
Lumsden, Andrew;
Simeone, Antonio
Regionalisation of anterior neuroectoderm and its competence in responding to forebrain and midbrain inducing activities depend on mutual antagonism between OTX2 and GBX2
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Medientyp:
E-Artikel
Titel:
Regionalisation of anterior neuroectoderm and its competence in responding to forebrain and midbrain inducing activities depend on mutual antagonism between OTX2 and GBX2
Beteiligte:
Martinez-Barbera, Juan Pedro;
Signore, Massimo;
Boyl, Pietro Pilo;
Puelles, Eduardo;
Acampora, Dario;
Gogoi, Robin;
Schubert, Frank;
Lumsden, Andrew;
Simeone, Antonio
Erschienen:
The Company of Biologists, 2001
Erschienen in:
Development, 128 (2001) 23, Seite 4789-4800
Beschreibung:
<jats:p>The anterior neural ridge (ANR), and the isthmic organiser (IsO) represent two signalling centres possessing organising properties necessary for forebrain (ANR) as well as midbrain and rostral hindbrain (IsO) development. An important mediator of ANR and IsO organising property is the signalling molecule FGF8. Previous work has indicated that correct positioning of the IsO and Fgf8 expression in this domain is controlled by the transcription factors Otx2 and Gbx2. In order to provide novel insights into the roles of Otx2 and Gbx2, we have studied mutant embryos carrying different dosages of Otx2, Otx1 and Gbx2. Embryos deficient for both OTX2 and GBX2 proteins (hOtx12/hOtx12; Gbx2–/–) show abnormal patterning of the anterior neural tissue, which is evident at the presomite-early somite stage prior to the onset of Fgf8 neuroectodermal expression. Indeed, hOtx12/hOtx12; Gbx2–/– embryos exhibit broad co-expression of early forebrain, midbrain and rostral hindbrain markers such as hOtx1, Gbx2, Pax2, En1 and Wnt1 and subsequently fail to activate forebrain and midbrain-specific gene expression. In this genetic context, Fgf8 is expressed throughout the entire anterior neural plate, thus indicating that its activation is independent of both OTX2 and GBX2 function. Analysis of hOtx12/hOtx12; Gbx2–/– and Otx1+/–; Otx2+/– mutant embryos also suggests that FGF8 cannot repress Otx2 without the participation of GBX2. Finally, we report that embryos carrying a single strong hypomorphic Otx2 allele (Otx2λ) in an Otx2 and Gbx2 null background (Otx2λ/–; Gbx2–/–) recover both the headless phenotype exhibited by Otx2λ/– embryos and forebrain- and midbrain-specific gene expression that is not observed in hOtx12/hOtx12; Gbx2–/– mutants. Together, these data provide novel genetic evidence indicating that OTX2 and GBX2 are required for proper segregation of early regional identities anterior and posterior to the mid-hindbrain boundary (MHB) and for conferring competence to the anterior neuroectoderm in responding to forebrain-, midbrain- and rostral hindbrain-inducing activities.</jats:p>