Animals have a specific body size for species. There are no elephant-size mouse and mouse-size elephant. How body sizes of animals are determined so exactly? In C. elegans, many body size mutants exist. Among them,
sma-1-9,
dbl-1 and
daf-4 cause small body size, when they are mutated. Most of them encode signaling proteins involved in TGF- pathway. In contrast,
egl-4 is a big-body-size mutant. By genetic analyses, EGL-4 is considered to negatively regulate DBL-1/ TGF- pathway. Other mutants,
lon-1, -2 and -3 are long-body-size mutants. Recently Morita et al. showed that
lon-1 gene expression was negatively regulated by DBL-1/TGF- pathway1). In
dbl-1 mutant, Morita et al. reported that
lon-1 mRNA level increased1). We measured
lon-1 mRNA level in
egl-4 mutant, by real-time PCR, and found that
lon-1 mRNA levels is decreased in
egl-4 mutant. This result is consistent with genetic analyses mentioned above. We also confirmed these phenomena with GFP driven by
lon-1 promoter (
lon-1p::gfp). In
egl-4 mutant, expression of
lon-1p::gfp decreased as expected, although, in
dbl-1 animals, we could not distinguish the expression from wild type. To identify genes upstream of
lon-1, we conducted screening of mutants with changed
lon-1p::gfp level. From 12,000 mutagenized genomes, we isolated 10 mutants with changed
lon-1::gfp level. Among them, 2 mutants with decreased
lon-1::gfp level exhibit large body size. This is consistent with an expectation, because
egl-4 mutant exhibit large body size. Positional cloning of one of them,
qj1, revealed that the gene is VW02B12L.4, which encodes a protein with no homologue in other species except in C. briggsae. Expression studies using a functional gfp translational fusion suggested that VW02B12L.4 is expressed in hypodermis, pharynx, seam cell and some neurons. GFP fusion protein was localized in nuclei of these tissues. To identify the function in body size regulation, we analyzed double mutants between
qj1 and other body size mutants. In
sma-2 or -3 background,
qj1 mutation did not cause any increase in body size of sma mutants, suggesting that VW02B12L.4 regulates negatively SMA-2 and SMA-3. On the other hand, in
dbl-1 background,
qj1 mutation increased the body size, suggesting VW02B12L.4 acts in parallel to DBL-1. We propose a model which VW02B12L.4 modifies Smads activity in nucleus and regulates the body size independently of DBL-1. 1) K. Morita, et al. (2002) EMBO. J, 21, 1063-1073