Binary cell fate specification during C. elegans embryogenesis driven by reiterated reciprocal asymmetry of TCF POP-1 and its coactivator beta-catenin SYS-1.
C. elegans embryos exhibit an invariant lineage comprised primarily of a stepwise binary diversification of anterior-posterior (A-P) blastomere identities. This binary cell fate specification requires input from both the Wnt and MAP kinase signaling pathways. The nuclear level of the TCF protein POP-1 is lowered in all posterior cells. We show here that the beta-catenin SYS-1 also exhibits reiterated asymmetry throughout multiple A-P divisions and that this asymmetry is reciprocal to that of POP-1. Furthermore, we show that SYS-1 functions as a coactivator for POP-1, and that the SYS-1-to-POP-1 ratio appears critical for both the anterior and posterior cell fates. A high ratio drives posterior cell fates, whereas a low ratio drives anterior cell fates. We show that the SYS-1 and POP-1 asymmetries are regulated independently, each by a subset of genes in the Wnt/MAP kinase pathways. We propose that two genetic pathways, one increasing SYS-1 and the other decreasing POP-1 levels, robustly elevate the SYS-1-to-POP-1 ratio in the posterior cell, thereby driving A-P differential cell fates.
Huang
Shuyi
S
Department of Molecular Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390, USA.
Shetty
Premnath
P
Robertson
Scott M
SM
Lin
Rueyling
R
D000818:Animals; D019521:Body Patterning; D017173:Caenorhabditis elegans / Q000196:embryology / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D006609:High Mobility Group Proteins / Q000235:genetics / Q000502:physiology*; D020935:MAP Kinase Signaling System; D009154:Mutation; D051820:TCF Transcription Factors / Q000235:genetics / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D051153:Wnt Proteins / Q000502:physiology; D051176:beta Catenin / Q000502:physiology*
D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; C502083:Sys-1 protein, C elegans; D051820:TCF Transcription Factors; D014157:Transcription Factors; D051153:Wnt Proteins; D051176:beta Catenin; C096787:pop-1 protein, C elegans