No abstract

The UNC-4 homeoprotein and the Groucho-like corepressor UNC-37 specify synaptic choice in the Caenorhabditis elegans motor neuron circuit. In unc-4 mutants, VA motor neurons are miswired with inputs from interneurons normally reserved for their lineal sisters, the VB motor neurons. Here we show that UNC-4 and UNC-37 function together in VA motor neurons to repress VB-specific genes and that this activity depends on physical contact between UNC-37 and a conserved Engrailed-like repressor domain (eh1) in UNC-4. Missense mutations in the UNC-4 eh1 domain disrupt interactions between UNC-4 and UNC-37 and result in the loss of UNC-4-dependent repressor activity in vivo. A compensatory amino acid substitution in UNC-37 suppresses specific unc-4 alleles by restoring physical interactions with UNC-4 as well as UNC-4-dependent repression of VB-specific genes. We propose that repression of VB-specific genes by UNC-4 and UNC-37 is necessary for the creation of wild-type inputs to VA motor neurons. The existence of mammalian homologs of UNC-4 and UNC-37 indicates that a similar mechanism could regulate synaptic choice in the vertebrate spinal cord.

No abstract

Abstract. To determine the biological role of transforming growth factor-@ (TGF-@) in mammary carcinomas in vim, estrogen-dependent MCF-7 cells were transfected with a mouse TGF-@I cDNA. Growth characteristics in culture were not altered in the transfected cells. However, the MCF-7/TGF-@1 cells formed tumors in ovariectomized athymic mice in the absence of estrogen supplementation. Daily injections of human recombinant TGF-@I supported tumor formation by wild-type MCF-7 cells in castrated nude mice in the absence of exogenous estradiol. In another approach to the same question, the effect of anti-TGF-@ antibodies on tumor formation by estrogen-independent MDA-231 cells was examined. The 2G7 IgG2b (2G7) antibody, which neutralizes TGF-@I, 42, and 43, blocked the formation of MDA-231 tumors at the injection site and lung metastases in nude mice. Inoculation of MDA-231 cells inhibited, while injection of 2G7 increased mouse spleen natural killer (NK) activity. 2G7 did not inhibit MDA-231 tumors and metastases in NK-deficient animals. Finally, medium conditioned by MDA-231 cells inhibited lymphocyte-mediated NK activity; this inhibition was abrogated by 2G7, but not by a control IgG2. These data support a positive role for tumor cell TGF-@ in the maintenance and/or progression of mammary carcinoma cells in an intact host.