High impact information on Otx2

• Brachyenteron activates the homeobox gene orthopedia in a dose-dependent manner via multiple binding sites with the consensus (A/G)(A/T)(A/T)NTN(A/G)CAC(C/T)T [1].
• At the molecular level, downregulation of Ras-dva inhibits the expression of several regulators of the anterior neural plate and folds patterning, such as Otx2, BF-1 (also known as Foxg1), Xag2, Pax6, Slug and Sox9, and interferes with FGF8 signaling within the anterior ectoderm [2].
• On its own, Six3 is unable to induce neural tissue in animal caps, but it can do so in combination with Otx2 [3].
• Other effects of the ectopic Xanf-1 include cyclopic phenotype and inhibition of the cement gland, both by Otx-2-dependent and -independent mechanisms [4].
• Activation of Otx-2, Pax-6 and Sox-3 in competent ectoderm occurs in response to the early inducing tissue, the anterior neural plate [5].

Biological context of Otx2

• We show that IGF pathway specifically induces the expression of Otx2 in the early gastrula and blocks convergent extension of neuroectoderm and mesoderm through the transcriptional activation of Otx2 gene [6].
• At the onset of organogenesis, ScOtx5 is transcribed over a broad domain spanning the whole prosencephalon and mesencephalon, albeit with a much lower signal intensity than its paralogues Otx1 and Otx2 [7].
• The Xvent family of homeobox transcription factors is essential for the establishment of the dorsal-ventral body axis during Xenopus embryogenesis [8].
• Sequence analysis of the mouse and human promoter region revealed the presence of two palindromic binding elements for homeobox genes of the prd type to which goosecoid belongs [9].
• DNA sequences mediating the transcriptional response of the Mix.2 homeobox gene to mesoderm induction [10].

Anatomical context of Otx2

• While both of these factors prevent the activation of genes specific to the nascent central nervous system, Msx1 inhibits anterior markers, including Otx2 and cement gland-specific genes [11].
• The border between the transcription domains of Otx2 and Gbx2 is the earliest known marker of the region where the midbrain/hindbrain boundary (MHB) organizer will develop [12].
• In addition, taking advantage of hormone-inducible versions of Xgbx2a and its antimorph, we show that the ability of Xgbx2a to induce head malformations is restricted to gastrula stages and correlates with its ability to repress Otx2 during the same developmental stages [12].
• In contrast, the overexpression of a dominant negative form of Nbx during neurula stages suppressed the expression of the neural crest marker Slug and expanded neural markers such as Otx2 and Sox2 [13].
• The homeobox gene goosecoid has been implicated to play a central role in the Spemann organizer tissue of the vertebrate embryo [9].

Associations of Otx2 with chemical compounds

• XA-1, Otx-2, X-Delta, and Xotch transcripts were not sensitive to noradrenaline [14].

Regulatory relationships of Otx2

• Otx2 represses the expression of Xbra and Xwnt-11, and the effects of IGF on gastrulation movements can be partially rescued by antisense Otx2 morpholino oligonucleotide [6].

Other interactions of Otx2

• Anterior-posterior patterning of the embryo requires the activity of multiple homeobox genes among them Hox, caudal (Cdx, Xcad) and Otx2 [12].
• Consistent with this, we show that inhibition of IGF signaling or Otx2 function induces Xbra and Xwnt11 expression and convergent extension in ectodermal cells [6].
• The circadian gene Clock is restricted to the anterior neural plate early in development and is regulated by the neural inducer noggin and the transcription factor Otx2 [15].
• Homeobox genes like Otx-2 and members of the Hox family have been implicated in this process [16].
• This later Eomes expression marks a very localized region of the forebrain distinct from that of Otx-2, anterior to that of En-1 and overlapping that of Sox-3 [17].

References