In vertebrates, BMP regulatory cascade is involved in the dorso-ventral pattern formation at the embryonic stage. Molecules such as chordin and collagen type IIA carrying a cysteine-rich vWC domain, antagonize the BMP signaling by binding to the BMP proteins. However, no chordin and collagen type IIA-like molecule is identified in C. elegans. Only two C. elegans vWC domain carrying genes B0024.14 and F19C6.3 are present in the whole genome. B0024.14 has an ortholog CRIM1 in mouse and human, while no F19C6.3 ortholog in vertebrate system has been found. The CRIM1 molecule is a novel transmembrane protein. There is a signal peptide at N-terminus. An insulin-like growth factor binding domain and six vWC domains are present. The CRIM1 gene is expressed in the brain, lens, heart, kidney, lung, pancreas, placenta, skeletal muscle and spinal cord in a pattern similar to that of BMP molecules. The relationship between CRIM1 and BMP is still unknown. The CRIM-like gene in C. elegans, B0024.14b, is primarily expressed in the pharyngeal bulb. Three additional transcripts have also been identified. These transcripts share the same 5' regulatory sequence and are detected in the neurons of pharyngeal bulb, gut near rectum, ventral nerve cord and some neurons in sensory rays. Another novel molecule F19C6.3 has a signal peptide, two vWC domains and two EGF-like domains. It is expressed in the neurons at the nerve ring, muscles near vulva and posterior region of the ventral nerve cord in adult male tail. The loss of function B0024.14 and F19C6.3 phenotypes have been examined by RNAi treatment. The body length of these animals is shortened by 10% as compared with wild type animals. Mutation in
dbl-1, a BMP-like molecule in worm, has been shown to have reduction in animal body length. We hypothesize that that these vWC genes may have an agonizing role in the
dbl-1 pathway. Epistatic analysis and examination the downstream target genes of
dbl-1 pathway in the background with a loss of vWC function is in progress to elucidate how these vWC molecules interact with the BMP-like pathways in C. elegans development.