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.
Foehr
Marisa L
ML
Department of Molecular Biology and Genetics, Cornell University, 439 Biotechnology Building, Ithaca, NY 14853, USA.
Liu
Jun
J
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