Disease relevance of chd

• Genomic organisation of the human chordin gene and mutation screening of candidate Cornelia de Lange syndrome genes [1].

High impact information on chd

• We generated phenocopies of mutations of the genes no tail (ref. 2), chordin (ref. 3), one-eyed-pinhead (ref. 4), nacre (ref. 5) and sparse (ref. 6), removing gene function from maternal through post-segmentation and organogenesis developmental stages [2].
• Through injections of chd mRNA into the early embryo, we restored wild-type gene expression patterns, and the resultant fish, although genotypically mutant, developed normal axial skeletons and fins [3].
• Some ventralized mutants recover and develop into fertile adults, thereby revealing a requirement for chd function for the later processes of fin and caudal skeletal patterning [3].
• Noggin antagonism is thought to prevent osteogenesis at sites of joint formation, whereas chordin has not yet been implicated in skeletogenesis [3].
• Our results demonstrate that chordin function during gastrulation is important for the correct morphogenesis of the adult zebrafish skeleton [3].

Biological context of chd

• Lastly we observed a striking increased penetrance of the swirl/bmp2b dominant dorsalized phenotype, when Chordin function is also absent [4].
• Loss of the BMP antagonist Chordin is expected to increase BMP signaling levels in a swirl heterozygote, but instead we observed an apparent decrease in BMP signaling levels and a loss of ventral tail tissue [4].
• While injection of BMP4 MO had no effect on WT hematopoiesis, co-injecting BMP4 with chd MOs significantly reduced ICM expansion [5].
• We show that this early restriction of Bmp gene expression, which occurs independently of noggin and chordin, is an essential step in the establishment of DV patterning [6].
• Embryonic patterning is highly sensitive to maternal and zygotic ogo gene dosage, especially when the level of zygotic chordin activity is also reduced [7].

Anatomical context of chd

• Our results suggest that by regulating the expression of her5, the Bmp2b/Chordin gradient directs the anteroposterior patterning of endoderm in zebrafish embryos [8].
• Furthermore, Chordin was degraded by COS cells expressing Tolloid [9].
• In the zygote, repression of ventralizing Bmp activity on the dorsal side through chordin and noggin is crucial for establishment of a dorsally located organizer [10].
• We demonstrate that Tld cleavage is crucial in restricting Chordin function in vivo, and is carried out by redundant enzymes in the zebrafish gastrula [11].
• We utilized zebrafish mutant combinations that disrupt Chordin and mesoderm formation to reveal additional signals that contribute to the establishment of the neural domain [12].

Enzymatic interactions of chd

• Thus, the Tolloid/Mini fin metalloprotease that normally cleaves and inhibits Chordin activity is dispensable, when Ogon antagonism is reduced [4].

Regulatory relationships of chd

• Misexpression of prdm1 inhibits the formation of dorsoanterior structures and reduces expression of chordin, which encodes a BMP antagonist [13].
• In turn, vox and vent repress chordin expression, restricting its function as an antagonist of ventral fates to the dorsal side of the embryo [14].

Other interactions of chd

• Overexpression of fgf17b dorsalizes zebrafish gastrulae by enhancing expression of chordin (chd), which is an antagonist of the ventralizing signals BMPs [15].
• We conclude that bmp1 and mfn gene products functionally overlap and are together responsible for a key portion of the Chordin processing activity necessary to formation of the zebrafish dorsoventral axis [16].
• Moreover, loss of tsg1 partially suppressed the ventralized phenotypes of mutants of the BMP antagonists Chordin or Sizzled (Ogon) [17].
• Specifically, Bone Morphogenetic Proteins (Bmps) pattern ventral tissues of the embryo while inhibitors of Bmps, such as Chordin, Noggin and Follistatin, are implicated in dorsal mesodermal and neural development [18].
• However, this effect was mediated by Chordino (zebrafish Chordin), because Fgf3 induces chordino expression in the epiblast and Fgf3-induced neural expansion was substantially suppressed in dino mutants with mutated chordino genes [19].

References