Dorsoventral patterning of the C. elegans postembryonic mesoderm requires both LIN-12/Notch and TGFbeta signaling.
The C. elegans postembryonic mesodermal lineage arises from a single cell M, which generates distinct dorsal and ventral cell types. We have previously shown that mutations in the Schnurri homolog sma-9 cause ventralization of the M lineage and that wild-type SMA-9 antagonizes the Sma/Mab TGFbeta pathway to promote dorsal M lineage fates [Foehr, M.L., Lindy, A.S., Fairbank, R.C., Amin, N.M., Xu, M., Yanowitz, J., Fire, A.Z., Liu, J., 2006. An antagonistic role for the C. elegans Schnurri homolog SMA-9 in modulating TGFbeta signaling during mesodermal patterning. Development 133, 2887-2896]. Interestingly, loss-of-function mutations in the Notch receptor lin-12 cause dorsalization of the M lineage [Greenwald, I.S., Sternberg, P.W., Horvitz, H.R., 1983. The lin-12 locus specifies cell fates in Caenorhabditis elegans. Cell 34, 435-444]. We have found that although LIN-12 protein is present in both the dorsal and ventral M lineage cells, its ligands LAG-2 and APX-1 are asymmetrically localized in cells adjacent to ventral M-derived cells, and may function redundantly in promoting ventral M lineage fates. To investigate how LIN-12/Notch signaling interacts with SMA-9 and Sma/Mab TGFbeta signaling in regulating M lineage patterning, we generated double and triple mutant combinations among lin-12, sma-9 and dbl-1 (the ligand for the Sma/Mab TGFbeta pathway) and examined their M lineage phenotypes. Our results suggest that the LIN-12/Notch pathway and the Sma/Mab TGFbeta pathway function independently in regulating dorsoventral patterning of the M lineage, with LIN-12/Notch required for ventral M lineage fates, and SMA-9 antagonism of TGFbeta signaling required for dorsal M lineage fates. Our work provides a model for how combined Notch and TGFbeta signaling regulates the developmental potential of two equipotent cells along the dorsoventral axis.
Department of Molecular Biology and Genetics, Cornell University, 439 Biotechnology Building, Ithaca, NY 14853, USA.
Marisa L
ML
Foehr
Jun
J
Liu
D000818:Animals; D019521:Body Patterning; D017173:Caenorhabditis elegans / Q000166:cytology / Q000254:growth & development*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008648:Mesoderm / Q000166:cytology*; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction; D015222:Sodium Channels / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; C082460:Lin-12 protein, C elegans; D008565:Membrane Proteins; D051880:Receptors, Notch; D015222:Sodium Channels; D016212:Transforming Growth Factor beta; C489774:apx-1 protein, C elegans; C484140:dsl-1 protein, C elegans; C086488:lag-2 protein, C elegans