Otx2 can activate the isthmic organizer genetic network in the Xenopus embryo

Tour, Ella; Pillemer, Graciela; Gruenbaum, Yosef; Fainsod, Abraham

doi:10.1016/s0925-4773(01)00591-3

Cited by 19 publications

(15 citation statements)

References 65 publications

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“…As expected Wnts were detected in additional regions (Figures 1 and 2) with some of them reported earlier [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30]: Wnt1 , Wnt2b , Wnt3a , Wnt8b , Wnt10a and Wnt10b are in the nervous system; Wnt5a , Wnt5b , Wnt7a , Wnt9a , Wnt11 , Wnt11b and Wnt16 are in the heart region; Wnt3a , Wnt7c , Wnt8a , Wnt8b , Wnt9a , Wnt9b and Wnt10b are in the epidermis; Wnt7a and Wnt7b are in the lateral plate mesoderm; Wnt11 and Wnt11b are in the somites; finally, Wnt3a and Wnt6 are in the ear.…”

Section: Resultssupporting

confidence: 87%

Expression of Wnt Signaling Components during Xenopus Pronephros Development

2011

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BackgroundThe formation of the vertebrate kidney is tightly regulated and relies on multiple evolutionarily conserved inductive events. These are present in the complex metanephric kidney of higher vertebrates, but also in the more primitive pronephric kidney functional in the larval stages of amphibians and fish. Wnts have long been viewed as central in this process. Canonical β-Catenin-dependent Wnt signaling establishes kidney progenitors and non-canonical β-Catenin-independent Wnt signaling participate in the morphogenetic processes that form the highly sophisticated nephron structure. While some individual Wnt signaling components have been studied extensively in the kidney, the overall pathway has not yet been analyzed in depth.Methodology/Principal FindingsHere we report a detailed expression analysis of all Wnt ligands, receptors and several downstream Wnt effectors during pronephros development in Xenopus laevis using in situ hybridization. Out of 19 Wnt ligands, only three, Wnt4, Wnt9a and Wnt11, are specifically expressed in the pronephros. Others such as Wnt8a are present, but in a broader domain comprising adjacent tissues in addition to the kidney. The same paradigm is observed for the Wnt receptors and its downstream signaling components. Fzd1, Fzd4, Fzd6, Fzd7, Fzd8 as well as Celsr1 and Prickle1 show distinct expression domains in the pronephric kidney, whereas the non-traditional Wnt receptors, Ror2 and Ryk, as well as the majority of the effector molecules are rather ubiquitous. In addition to this spatial regulation, the timing of expression is also tightly regulated. In particular, non-canonical Wnt signaling seems to be restricted to later stages of pronephros development.Conclusion/SignificanceTogether these data suggest a complex cross talk between canonical and non-canonical Wnt signaling is required to establish a functional pronephric kidney.

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Section: Resultssupporting

confidence: 87%

Expression of Wnt Signaling Components during Xenopus Pronephros Development

2011

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“…3 ). Although in vertebrates, ectopic expression of Otx alone can activate the expression of several of these MHB markers (i.e., en2 , Wnt1 , Pax2 , Fgf8 and Gbx2 ) [Tour et al, 2002], in amphioxus, only Fgf8/17/18 among these genes is co-expressed with Otx [Meulemans and Bronner-Fraser, 2007] ( fig. 3 ).…”

Section: Patterning Of the Neural Plate Is Comparable In Amphioxus Anmentioning

confidence: 99%

“…In amphioxus, Fgf/17/18 and Pax2/5/8 are expressed in the Otx and Gbx zones respectively, and co-option of Wnt1 for a role in the midbrain might have influenced the expression of both. Several genes, including Lmx1b and Pbx , which may cooperate with en to regulate expression of Wnt1 [Tour et al, 2002;Erickson et al, 2007;Guo et al, 2007]. Expression of other vertebrate MHB markers such as Pbx and Lmx1b has not been determined in amphioxus, and therefore, the possibility remains that these genes might also have been co-opted for roles in the MHB gene network subsequent to genome duplications.…”

Section: Neofunctionalization and Recruitment Of Genes Into Gene Netwmentioning

confidence: 99%

Gene Duplication, Co-Option and Recruitment during the Origin of the Vertebrate Brain from the Invertebrate Chordate Brain

Holland

Short

2008

Brain Behav Evol

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The brain of the basal chordate amphioxus has been compared to the vertebrate diencephalic forebrain, midbrain, hindbrain and spinal cord on the basis of the cell architecture from serial electron micrographs and patterns of developmental gene expression. In addition, genes specifying the neural plate and neural plate border as well as Gbx and Otx, that position the midbrain/hindbrain boundary (MHB), are expressed in comparable patterns in amphioxus and vertebrates. However, migratory neural crest is lacking in amphioxus, and although it has homologs of the genes that specify neural crest, they are not expressed at the edges of the amphioxus neural plate. Similarly, amphioxus has the genes that specify organizer properties of the MHB, but they are not expressed at the Gbx/Otx boundary as in vertebrates. Thus, the genetic machinery that created migratory neural crest and an MHB organizer was present in the ancestral chordate, but only co-opted for these new roles in vertebrates. Analyses with the amphioxus genome project strongly support the idea of two rounds of whole genome duplication with subsequent gene losses in the vertebrate lineage. Duplicates of developmental genes were preferentially retained. Although some genes apparently acquired roles in neural crest prior to these genome duplications, other key genes (e.g., FoxD3 in neural crest and Wnt1 at the MHB) were recruited into the respective gene networks after one or both genome duplications, suggesting that such an expansion of the genetic toolkit was critical for the evolution of these structures. The toolkit has also increased by alternative splicing. Contrary to the general rule, for at least one gene family with key roles in neural crest and the MHB, namely Pax genes, alternative splicing has not decreased subsequent to gene duplication. Thus, vertebrates have a much larger number of proteins available for mediating new functions in these tissues. The creation of new splice forms typically changes protein structure more than evolution of the protein after gene duplication. The functions of particular isoforms of key proteins expressed at the MHB and in neural crest have only just begun to be studied. Their roles in modulating gene networks may turn out to rival gene duplication for facilitating the evolution of structures such as neural crest and the MHB.

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“…Moreover, the FM enhancer is conserved among vertebrate Otx2 orthologues, from skate to mammal and teleost orthologues, but the FM2 enhancer is unique to rodent Otx2 orthologues (28,30). The antagonistic interaction between Otx2 and Gbx has been suggested not only in mice, but also in chicks (19,24), Xenopus (61,62), and zebrafish (11,25). Therefore, it is probable that the FM enhancer is the target of the Gbx2 regulation of the Otx2 expression for MHB formation.…”

mentioning

confidence: 99%

Gbx2 Directly Restricts Otx2 Expression to Forebrain and Midbrain, Competing with Class III POU Factors

Inoue¹,

Kurokawa

Takahashi³

et al. 2012

Molecular and Cellular Biology

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bOtx2 plays essential roles in rostral brain development, and its counteraction with Gbx2 has been suggested to determine the midbrain-hindbrain boundary (MHB) in vertebrates. We previously identified the FM enhancer that is conserved among vertebrates and drives Otx2 transcription in forebrain/midbrain from the early somite stage. In this study, we found that the POU homeodomain of class III POU factors (Brn1, Brn2, Brn4, and Oct6) associates with noncanonical target sequence TAATTA in the FM enhancer. MicroRNA-mediated knockdown of Brn2 and Oct6 diminished the FM enhancer activity in anterior neural progenitor cells (NPCs) differentiated from P19 cells. The class III POU factors associate with the FM enhancer in forebrain and midbrain but not in hindbrain. We also demonstrated that the Gbx2 homeodomain recognizes the same target TAATTA in the FM enhancer, and Gbx2 associates with the FM enhancer in hindbrain. Gbx2 misexpression in the anterior NPCs repressed the FM enhancer activity and inhibited Brn2 association with the enhancer, whereas Gbx2 knockdown caused ectopic Brn2 association in the posterior NPCs. These results suggest that class III POU factors and Gbx2 share the same target site, TAATTA, in the FM enhancer and that their region-specific binding restricts Otx2 expression at the MHB. One of the most important events in the initial brain regionalization is the formation of the midbrain-hindbrain boundary (MHB), where isthmus, a local organizer for midbrain and hindbrain development, is formed. A homeobox transcription factor gene, Otx2, plays essential roles in the formation and patterning of the rostral brain, while a homeobox gene, Gbx2, does so in caudal brain development (2,12,56,65). Their expression initially overlaps, but segregates around the 6-somite stage; the mutual suppression between them has been suggested to establish the MHB at embryonic day 8.5 (E8.5) and to maintain the isthmic structure at later stages (23, 53); however, the details of the molecular mechanisms of the suppressive interaction between the Otx2 and Gbx2 genes remain to be determined.We have made efforts to elucidate the molecular mechanisms of the transcriptional regulation of the Otx2 gene and identified a series of cis-regulatory elements (26,(28)(29)(30)(31). Among these, the Otx2 expression in the anterior neural plate at the presomite stage is regulated by the AN enhancer, which is located 90 kb upstream (31, 60); its activity covers the entire anterior neural plate, the caudal limits being obscured and overlapping with the anterior part of the Gbx2 expression. The AN enhancer loses its activity at an early somite stage, and the subsequent Otx2 expression in rostral brain is regulated by the FM and FM2 enhancers, which are located 75 kb upstream and 115 kb downstream, respectively (28). The FM and FM2 enhancers lack activities in the most rostral part that correspond to future telencephalon and hypothalamus, and the caudal limit of their activities coincides with the MHB. Genetic analysis by enhancer mutants sugge...

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Otx2 can activate the isthmic organizer genetic network in the Xenopus embryo

Cited by 19 publications

References 65 publications

Expression of Wnt Signaling Components during Xenopus Pronephros Development

Expression of Wnt Signaling Components during Xenopus Pronephros Development

Gene Duplication, Co-Option and Recruitment during the Origin of the Vertebrate Brain from the Invertebrate Chordate Brain

Gbx2 Directly Restricts Otx2 Expression to Forebrain and Midbrain, Competing with Class III POU Factors

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