Role of T-box gene tbx-2 for anterior foregut muscle development in C-elegans

During organogenesis, pluripotent precursor cells acquire a defined identity such as Muscle or nerve. The transition from naive precursor towards the differentiated state is characterized by sequential waves of gene expression that are determined by regulatory transcription factors. A key question is how transcriptional circuitry dictates the succession of events that accompanies developmental competence, cell fate specification and differentiation. To address this question, we have examined how anterior muscles are established within the Caenorhahditis elegans foregut (pharynx). We find that the T-box transcription factor tbx-2 is essential to form anterior pharyngeal muscles from the ABa blastomere. In the absence of tbx-2 function, ABa-derived cells initiate development normally: they receive glp-l/Notch signaling cues, activate the T-box gene TBX-38 and express the organ selector gene PHA-4/FoxA. However, these cells subsequently arrest development, extinguish PHA-4 and fail to activate PHA-4 target genes. tbx-2 mutant cells do not undergo apoptosis and there is no evidence for adoption of an alternative fate. TBX-2 is expressed in ABa descendants and depends on activation by pha-4 and repression by components of glp-l/Notch signaling. Our analysis suggests that a positive feedback loop between tbx-2 and pha-4 is required for ABa-derived precursors to commit to pharyngeal muscle fate. (c) 2006 Elsevier Inc. All rights reserved.