Disease relevance of CHRD

• In osteoarthritis, chordin was also found in the superficial layers (8.9 (1.1)%), though at a significantly higher level (24.7 (1.5)%) in the last two thirds of the cartilage [1].

High impact information on CHRD

• Cleavage of Chordin by Xolloid metalloprotease suggests a role for proteolytic processing in the regulation of Spemann organizer activity [2].
• Co-injection of sub-inhibitory levels of morpholines directed against both Tsg and chordin synergistically enhances the penetrance of the ventralized phenotype [3].
• They are the components of the Spemann organizer, noggin, chordin, and follistatin, members of the Dan/Cerberus family, and twisted gastrulation [4].
• Downstream of these events, chordin and bone morphogenetic protein acting within the central disc may play mutually opposing roles influencing streak formation [5].
• Biglycan is a new extracellular component of the Chordin-BMP4 signaling pathway [6].

Biological context of CHRD

• We have found that CHRD is expressed in fetal as well as in adult tissues with relatively high levels in liver, cerebellum and female genital tract, suggesting functions in late embryogenesis and adult physiology [7].
• Chrd was mapped to mouse chromosome 16 using interspecific crosses, and the cognate human gene CHRD was localized to human chromosome 3q27 by radiation hybrid mapping [8].
• To study factors involved in chromoplast biogenesis in floral tissues, a minor (in abundance) protein of about 14 kD, CHRD (chromoplast protein D), was isolated from cucumber corolla chromoplasts [9].
• CHRD, a plant member of the evolutionarily conserved YjgF family, influences photosynthesis and chromoplastogenesis [10].
• Chordin is expressed throughout the axial mesoderm as it extends, but is downregulated in prechordal mesoderm coincident with the onset of RDVM cell differentiation [11].

Anatomical context of CHRD

• The evolutionary conservation of Chordin/bone morphogenetic protein (BMP) signaling supports the hypothesis of dorsal-ventral axis inversion of vertebrates and invertebrates, and implies that the invention of a central nervous system occurred only once during animal evolution [12].
• FRL-1MO also inhibited the expression of these genes in dorsal ectoderm, but did not affect the expression of chordin, which acts as a neural inducer from dorsal mesoderm [13].
• High affinity binding of Chd sequesters the BMP ligands in the extracellular space, preventing interactions with their membrane receptors [7].
• Unexpectedly, chordin overexpression reduced formation of both primary and secondary notochord [14].
• (3) At the tailbud stage, among these pigment cell precursors, BMPb induces the differentiation of specifically the anterior type of pigment cell, the otolith; while posteriorly, CHORDIN suppresses BMP activity and allows ocellus differentiation [15].

Associations of CHRD with chemical compounds

• Based on the size of the cystine ring, these proteins were divided into three subfamilies: CAN (eight-membered ring), twisted gastrulation (nine-membered ring), as well as chordin and noggin (10-membered ring) [16].
• Gibberellic acid rapidly enhanced, whereas paclobutrazol down-regulated, the steady-state level of CHRD [9].
• This site lies within a proteinase-resistant fragment of chordin, presumably a glycopeptide, of molecular mass between 2 and 10 kDa [17].
• In a search for antigens immunologically related to chordin, a notochord-specific glycoprotein of sturgeneous fishes, extracts from 55 samples of human and rabbit tissues were tested for inhibition of [125I]chordin binding to rabbit polyclonal antibodies [18].

Enzymatic interactions of CHRD

• Further studies showed that PCPE-1 had no effect on the ability of BMP-1 to cleave chordin [19].

Regulatory relationships of CHRD

• Further, treating cultured chondrocytes with chordin interfered with maturation induced by treatment with BMP-2 [20].

Other interactions of CHRD

• The CHRD and THPO genes are very close neighbours and are transcribed from opposing DNA strands from promoters that are spaced less than 2 kb apart [21].
• However, mutation screening failed to identify CDLS patient-specific mutations in CHRD, GSC or SOX2 [21].
• Consistent with this, morpholino-injected embryos have ventrally expanded chordin expression and reduced activation of the Bmp-dependent transcription factors Smad1/5/8 [22].
• Outside the cell, soluble inhibitory proteins such as noggin, chordin, and follistatin can bind certain of the BMPs and inhibit their binding to cell surface receptors [23].
• For example, the regulators of BMPs that include noggin, chordin, cerberus, dan, and gremlin may be harnessed as therapies to offset calcification encountered after total hip arthroplasties [24].

Analytical, diagnostic and therapeutic context of CHRD

• Using RT-PCR, we showed that the LDMZ expressed gsc, lim-1, chordin, and noggin, but not the mesoderm marker bra [25].
• METHODS: Localisation of chordin in tissues was undertaken by immunohistochemistry and gene regulation was determined by real time polymerase chain reaction [1].

References