High impact information on ndr2

• An identical phenotype is displayed by double mutants for the nodal-related genes squint and cyclops [1].
• Here we test the morphogen properties of Cyclops and Squint-two Nodal-related transforming growth factor-beta signals required for mesoderm formation and patterning in zebrafish [2].
• Injection of cyc RNA non-autonomously restores sonic hedgehog-expressing cells of the ventral brain and floorplate that are absent in cyc mutants, whereas inducing activities are abolished by cyc, a mutation of a conserved cysteine in the mature ligand [3].
• The cyclops mutation blocks specification of the floor plate of the zebrafish central nervous system [4].
• Moreover, ectopic expression of PKI partially rescues somite and optic stalk defects in no tail and cyclops mutants that lack midline structures that normally synthesize Shh [5].

Biological context of ndr2

• Dorsal expression of cyclops requires Nodal-dependent autoregulation, whereas other factors induce cyclops expression in ventrolateral cells [6].
• One-eyed pinhead regulates cell motility independent of Squint/Cyclops signaling [7].
• Genes dependent on zebrafish cyclops function identified by AFLP differential gene expression screen [8].
• The transgene is ectopically activated by FoxA2, and expression of FoxA2 leads to rescue of floor plate differentiation in mutant embryos that are deficient in Cyclops signalling [9].
• A floor plate enhancer of the zebrafish netrin1 gene requires Cyclops (Nodal) signalling and the winged helix transcription factor FoxA2 [9].

Anatomical context of ndr2

• In double mutants for the zebrafish nodal-related genes squint (sqt) and cyclops (cyc) [3] [4] [5], dorsal marginal cells adopt neural fates, whereas in wild-type embryos, cells at this position form endoderm and axial mesoderm [10].
• In contrast, while Znr1/Cyclops reproducibly induces mesodermal and neural markers, it is an inefficient inducer of organizer-type mesoderm [11].
• In addition, zebrafish fast is also expressed bilaterally in the dorsal diencephalon, where the nodal-related cyclops gene is only expressed on the left side [12].
• The nodal-related genes cyclops and squint are expressed at the blastoderm margin and are required for prechordal plate and notochord formation [13].
• The first gene, crestin, is expressed predominantly in premigratory and migrating neural crest cells during somitogenesis stages. crestin expression is reduced in cyc mutants initially but recovers by late somitogenesis [8].

Associations of ndr2 with chemical compounds

• Zebrafish crestin was identified in a screen for genes dependent on cyclops function and is a member of a family of retroelements (Rubinstein et al. [2000] Genesis 26:86-97) [14].
• Inhibition of the endoplasmic reticulum Ca(2+) pump during early gastrulation induces cyclopia, mimicking defects observed in cyclops, squint, one-eyed pinhead, and silberblick mutant embryos [15].

Regulatory relationships of ndr2

• Zebrafish cyclops regulates the expression of shh in the ventral neural tube [16].
• Because col2a1 expression reveals abnormalities in the notochord of cyclopsb16 embryos, and less col2a1-expressing mesenchyme accumulates rostral to the notochord in cyclops embryos, the effects of the cyclopsb16 mutation are not confined to the central nervous system [17].

Other interactions of ndr2

• Overexpression of truncated smad2 in cyclops mutant embryos leads to a rescue of the eye and floorplate defects [18].
• Furthermore, we find that Cyclops is specifically required for the maintenance of lefty1 and lefty2 transcription [19].
• In embryos lacking both squint and cyclops, members of the nodal group of TGF-beta related molecules, gata5 expression in the blastoderm is abolished, making these factors primary candidates for the endogenous TGF-beta signal inducing gata5 [20].
• In zebrafish, mesoderm and endoderm formation requires the Nodal signals Cyclops and Squint and their cofactor One-eyed pinhead (Oep) [10-14] [21].
• Zebrafish calreticulin is highly expressed in the hatching gland and in the floor plate, tissues that are affected in cyc mutants [8].

Analytical, diagnostic and therapeutic context of ndr2

• Although a faint ndr2 mRNA signal was detected by RT-PCR in early embryos, no ndr2 mRNA was detected by whole-mount in situ hybridization in embryos up to 72 hpf, suggesting that it is expressed rather late [22].
• Based on sequence analysis and in accordance to zebrafish orthologues we named the isolated genes Ndr1, Ndr2 and Spaw [23].
• In situ hybridization analysis of the zebrafish cyclops mutants, lacking the midline floor plate cells, showed normal expression of tn-c mRNA in all trunk structures [24].

References