Question

1. What is known about the C. elegans gene ceh22?
2. What is known about the C. elegans gene skn-1?
3. What is known about the C. elegans gene apx-1?

Answer 1

The Caenorhabditis elegans NK-2 class homeoprotein CEH-22 is involved in combinatorial activation of gene expression in pharyngeal muscle.

The pharyngeal muscles of Caenorhabditis elegans are single sarcomere muscles used for feeding. Like vertebrate cardiac and smooth muscles, C. elegans pharyngeal muscle does not express any of the known members of the MyoD family of myogenic factors. To identify mechanisms regulating gene expression in this tissue, we have characterized a pharyngeal muscle-specific enhancer from myo-2, a myosin heavy chain gene expressed exclusively in pharyngeal muscle. Assaying enhancer function in transgenic animals, we identified three subelements, designated A, B and C, that contribute to myo-2 enhancer activity. These subelements are individually inactive; however, any combination of two or more subelements forms a functional enhancer. The B and C subelements have distinct cell type specificities. A duplication of B activates transcription in a subset of pharyngeal muscles (m3, m4, m5 and m7). A duplication of C activates transcription in all pharyngeal cells, muscle and non-muscle. Thus, the activity of the myo-2 enhancer is regulated by a combination of pharyngeal muscle-type-specific and organ-specific signals. Screening a cDNA expression library, we identified a gene encoding an NK-2 class homeodomain protein, CEH-22, that specifically binds a site necessary for activity of the B subelement. CEH-22 protein is first expressed prior to myogenic differentiation and is present in the same subset of pharyngeal muscles in which B is active. Expression continues throughout embryonic and larval development. This expression pattern suggests CEH-22 plays a key role in pharyngeal muscle-specific activity of the myo-2 enhancer.

SKN-1/Nrf, stress responses, and aging in Caenorhabditis elegans

The mammalian Nrf/CNC proteins (Nrf1, Nrf2, Nrf3, p45 NF-E2) perform a wide range of cellular protective and maintenance functions. The most thoroughly described of these proteins, Nrf2, is best known as a regulator of antioxidant and xenobiotic defense, but more recently has been implicated in additional functions that include proteostasis and metabolic regulation. In the nematode Caenorhabditis elegans, which offers many advantages for genetic analyses, the Nrf/CNC proteins are represented by their ortholog SKN-1. Although SKN-1 has diverged in aspects of how it binds DNA, it exhibits remarkable functional conservation with Nrf/CNC proteins in other species and regulates many of the same target gene families. C. elegans may therefore have considerable predictive value as a discovery model for understanding how mammalian Nrf/CNC proteins function and are regulated in vivo. Work in C. elegans indicates that SKN-1 regulation is surprisingly complex and is influenced by numerous growth, nutrient, and metabolic signals. SKN-1 is also involved in a wide range of homeostatic functions that extend well beyond the canonical Nrf2 function in responses to acute stress. Importantly, SKN-1 plays a central role in diverse genetic and pharmacologic interventions that promote C. elegans longevity, suggesting that mechanisms regulated by SKN-1 may be of conserved importance in aging. These C. elegans studies predict that mammalian Nrf/CNC protein functions and regulation may be similarly complex and that the proteins and processes that they regulate are likely to have a major influence on mammalian life- and healthspan.

Caenorhabditis elegans essential gene apx-1, encoding ARG-1 family member, Anterior Pharynx in eXcess.

apx-1 encodes one of ten C. elegans DSL (Delta, Serrate, LAG-2) proteins, integral transmembrane and secreted proteins that function as signaling ligands for the Notch family receptors GLP-1 and LIN-12; in the 4-cell embryo, maternally supplied APX-1 functions as a GLP-1 ligand for an inductive interaction that specifies the fate of the ABp blastomere; later in embryogenesis, APX-1 is required for formation of the LIN-12-dependent, invariant asymmetrical twist that occurs as part of normal gut morphogenesis; during larval development, APX-1 is required redundantly with DSL-1 and LAG-2 for the LIN-12-mediated lateral signal that spatially patterns the primary and secondary vulval cell lineages; in the early embryo, APX-1 is first detected at the anterior edge of the P1 blastomere, with later expression visible in P2 at sites of contact with ABp, and in the cytoplasm of the EMS and P3 blastomeres; expression in the vulval precursor cells (VPCs) is detected in the primary VPC, P6.p, and its descendants; embryonic APX-1 expression is dependent upon PIE-1 activity, while later vulval expression is mediated by the Ras signaling pathway and the SUR-2 transcriptional cofactor.
Wormbase predicts one model, but Caenorhabditis elegans cDNA sequences in GenBank, dbEST, Trace and SRA, filtered against clone rearrangements, coaligned on the genome and clustered in a minimal non-redundant way by the manually supervised AceView program, support at least 2 spliced variants.