Organ development can be divided into two phases known as the restrictive phase, when cells become determined to adopt an organ-specific fate, and the expressive phase, when cells comprising the organ acquire their cell-specific identities. Accordingly, among the genes known to control pharynx development in C. elegans are those required to establish organ identity and those involved in pharynx differentiation. The regulatory mechanisms that coordinate development between different organs are not well understood. To illuminate how late organ development is achieved and to understand the coordination of regulatory mechanisms involved in development of the pharynx and epidermis, we have isolated and characterized a zygotic embryonic lethal mutant, p harynx and el ongation defective ( pel-2 ). pel-2 mutations result in a block in terminal differentiation of the pharynx, as well as a failure to express the pharynx differentiation-promoting factor PHA-1 and to maintain expression of the pharynx identity factor, PHA-4. These findings imply that pel-2 acts within the pathway that regulates pharynx organ identity and differentiation. pel-2 mutants also fail to express several epidermal genes in the epidermis and show ectopic expression of the same genes in the pharynx, suggesting that PEL-2 is required reciprocally to activate epidermal genes in the epidermis and to repress them in the pharynx. We mapped pel-2 to the right end of chromosome IV and found that YAC Y73F8A rescued the embryonic lethality associated with the pel-2 mutation. Single gene rescue experiments revealed that the gene Y73F8A.34, defined by expressed sequence tags, also rescues embryonic lethality of different pel-2 alleles. RNAi of two non-overlapping regions of Y73F8A.34 phenocopies the pel-2 mutation, lending further support that this gene is pel-2 . However, efforts to identify the molecular lesion in this gene from pel-2 mutants have not yet been successful. Y73F8A.34 encodes a novel cysteine-rich domain, C6HC or DRIL motif, flanked by two Zn-binding RING fingers of the TRIAD (two RING fingers and DRIL) class of proteins, suggesting that it might perform a novel function in pharynx development (Van der Reijden et al., 1999). To determine the spatial and temporal expression pattern of Y73F8A.34, we analyzed expression pattern of three integrated transcriptional reporters. Expression is first detected at about 200 min. after fertilization, when there are 27 pharyngeal precursors. This observation is consistent with our finding that pel-2 is required for normal expression of pha-1 and pha-4 at this early stage. Expression of this putative pel-2 gene in pharyngeal cells continues throughout embryogenesis and appears to increase as development proceeds. Expression in the pharynx persists into adulthood and is also detected in the gut. The 5'regulatory region of the Y73F8A.34 gene contains five putative PHA-4 binding sites (Gaudet and Mango, 2002), suggesting that Y73F8A.34 is likely to be regulated by PHA-4. Further studies are directed at understanding the role of this gene in the regulatory pathway for pharynx development and epidermal differentiation. B. A. Van der Reijden , C. A. J. Erpelinck-Verschueren, B.Lowenberg and J.H. Jansen Protein Science 8 :1557-1561 (1999). J. Gaudet and S. Mango Science 295 :821-825 (2002).