High impact information on chrd

• In the absence of mesoderm, expression of Chordin and Noggin in ectoderm is required for anterior CNS formation [1].
• Here we demonstrate that sog, which is expressed in the ventrolateral region of the embryo that gives rise to the nerve cord, is functionally homologous to the chordin gene of Xenopus, which is expressed in the dorsal blastopore lip of the embryo and in dorsal mesoderm, in particular the notochord [2].
• Chd is sufficient to activate Kielin expression in mesoderm whereas Shh or HNF-3beta in addition to Chd is required for induction in ectoderm [3].
• Inhibition of Smicl function by means of antisense morpholino oligonucleotides causes the specific downregulation of Chordin, a dorsally expressed gene encoding a secreted BMP inhibitor that is involved in mesodermal patterning and neural induction [4].
• We show that the pro-apoptotic activity of Barhl2 is essential during normal neural plate formation as it limits the number of chordin- and Xshh-expressing cells in the prospective notochord and floorplate, which act as organizing centers [5].

Biological context of chrd

• In a differential screen for downstream genes of the neural inducers, we identified two extremely early neural genes induced by Chordin and suppressed by BMP-4: Zic-related-1 (Zic-r1), a zinc finger factor related to the Drosophila pair-rule gene odd-paired, and Sox-2, a Sry-related HMG factor [6].
• Integrin-alpha3 mediates binding of Chordin to the cell surface and promotes its endocytosis [7].
• These data and previous studies on ectoderm and endoderm (Sasai et al. [1995] Nature 377:757) support the idea that chordin functions as an anteriorizing signal in patterning the germ layers during vertebrate embryogenesis [8].

Anatomical context of chrd

• Twisted gastrulation is required for forebrain specification and cooperates with Chordin to inhibit BMP signaling during X. tropicalis gastrulation [9].
• In amniotes, like the amphibian Xenopus laevis, BMPs promote ventral specification, while chordin and other BMP inhibitors expressed dorsally in the Spemann's organizer play roles in establishment and/or maintenance of this region as dorsal endomesoderm [10].
• We find, however, that chordin-induced neural plate tissue can be induced to adopt neural crest fates by members of the FGF and Wnt families, growth factors that have previously been shown to posteriorize induced neural tissue [11].
• Our data support the hypothesis that chordin directs the formation of anterior somites that in turn are necessary for pronephros development [8].
• In RT-PCR analysis, the expression of dorsal gene, chordin was activated in the explants isolated after time 4.0 (about the 4000-cell stage which corresponds to the mid blastula transition (MBT)) at control stage 10 [12].

Associations of chrd with chemical compounds

• Xrx1 is activated by chordin and Hedgehog gene signaling, which induce anterior and proliferative fate, and is repressed by the differentiation-promoting activity of neurogenin and retinoic acid [13].
• Sog and its vertebrate counterpart Chordin contain four copies of a cysteine repeat (CR) motif defined by 10 cysteine residues spaced in a fixed pattern and a tryptophan residue situated between the first two cysteines [14].
• In a previous study, we demonstrated that FGFR1 activity within the organizer is required for the production of both the somitic muscle- and pronephros-patterning signals by the organizer and the expression of chordin, an organizer-specific secreted protein (Mitchell and Sheets [2001] Dev. Biol. 237:295-305) [8].

Analytical, diagnostic and therapeutic context of chrd

• Unexpectedly, transplantations into the dorsal side revealed a cell-autonomous requirement of Chordin for neural plate differentiation [15].

References