Transcription regulatory networks in Caenorhabditis elegans

zyg-9 encodes a predicted microtubule-association protein (MAP) of the XMAP215 family; during early embryonic development, maternal zyg-9 activity is required for microtubule-dependent processes such as meiotic and mitotic spindle organization and pronuclear migration; further, zyg-9 is essential for formation of long astral microtubules; ZYG-9 is required for centrosomal localization of TAC-1, the sole C. elegans TACC family member, with which it interacts, and mutually stabilizes, in vivo; in early embryos, ZYG-9 localizes to the meiotic spindle and spindle poles, as well as to mitotic centrosomes; during metaphase and anaphase ZYG-9 localizes to the central spindle region, and during interphase ZYG-9 is cytoplasmic; proper localization of ZYG-9 to the meiotic spindle is dependent upon wild-type activity of MEI-1, an ATPase essential for meiotic spindle formation, while proper localization of ZYG-9 to centrosomes is dependent, at least in part, upon TAC-1.

zmp-3 encodes a protein with two C-terminal noncanonical C2H2 zinc-fingers whose paralogs include HIM-8, ZIM-1/-2, and C02F5.12; ZIM-3 is specifically required for homolog pairing, synapsis, and segregation of chromosomes I and IV during meiosis; zim-3(tm2303) oocytes ending prophase have ~4 bivalents and ~4 univalents, the latter of which are consistently chromosomes I and IV; ZIM-3 associates with the right end of chromosome I and the left end of chromosome IV, which may indicate an association with their pairing centers; while the C-terminal region of ZIM-3 most closely resembles those of its orthologs in other Caenorhabditis species, its N-terminal region instead most closely resembles those of its paralogs in C. elegans, indicating coevolving, species-specific functions; ZIM-3 foci, like HIM-8 foci, associate with the nuclear envelope during meiotic prophase; zim-3 mutants also have some defective segregation of the X chromosome (yielding a Him phenotype), but this may be an indirect effect of autosomal asynapsis.

ZK829.4 is orthologous to the human gene GLYCINE DECARBOXYLASE PRECURSOR (GLUD1; OMIM:238300), which when mutated leads to disease.

ZK686.3 is orthologous to the putative tumor suppressor N33 (OMIM:601385, associated with homozygous deletion in metastatic prostate cancer and with loss of function in other tumors); ZK686.3 is also homologous to the S. cerevisiae dolichyl-diphosphooligosaccharide-protein glycotransferase gamma chain (34-kD) subunit, OST3.

ZK673.3 encodes a protein with a THAP or THAP-like domain required for embryonic development; other proteins with THAP or THAP-like domains include LIN-15A, LIN-15B, LIN-36, and HIM-17 (which all interact with LIN-35/Rb), as well as CDC-14B, CTB-1, GON-14, and ~100 other proteins such as Drosophila P element transposase and human nuclear proapoptotic factor THAP1.

ZK20.6 encodes a neprilysin; neprilysins are thermolysin-like zinc metallopeptidases, found on the outer surface of animal cells, that negatively regulate small signalling peptides (e.g., enkephalin, tachykinin, insulin, and natriuretic peptides) by cleaving them; ZK20.6 is closely paralogous to F18A12.8, and orthologous to CG9761 in Drosophila melanogaster; more generally, ZK20.6 falls into a group of proteins that includes the classical neprilysins found in mammals (e.g., PEX [OMIM:307800] and the enkephalin cleaving enzymes).

zip-5 encodes a bZip transcription factor; a zip-5::gfp promoter reporter gene fusion is expressed primarily in the nervous system, with mid- and late-stage embryos showing strong expression in head neurons, while larvae show expression in the ventral nerve cord and head and tail neurons; adults also show GFP expression in head muscles and intermittently in the intestine.

zip-3 encodes a bZip transcription factor.

zim-2 encodes a protein with two C-terminal noncanonical C2H2 zinc-fingers whose paralogs include HIM-8, ZIM-1, ZIM-3, and C02F5.12; ZIM-2 is specifically required for homolog pairing, synapsis, and segregation of chromosome V during meiosis; zim-2(tm574) oocytes ending prophase have ~5 bivalents and ~2 univalents, the latter of which are consistently chromosome V; zim-2 oocytes fail to begin chromosome V pairing at the start of meiosis; ZIM-2 associates with the right end of chromosome V, which may indicate an association with its pairing center; while the C-terminal region of ZIM-2 most closely resembles those of its orthologs in other Caenorhabditis species, its N-terminal region instead most closely resembles those of its paralogs in C. elegans, indicating coevolving, species-specific functions; ZIM-2 foci, like HIM-8 foci, associate with the nuclear envelope during meiotic prophase; zim-2 mutants also have some defective segregation of the X chromosome (yielding a Him phenotype), but this may be an indirect effect of autosomal asynapsis.

zig-4 encodes a predicted secreted protein that is a member of the immunoglobulin superfamily of proteins; ZIG-4 activity is required for maintenance of ventral nerve cord organization: the AVKL/R and PVQL/R axons of the left and right ventral nerve cords do not maintain their proper spatial positions and drift into the opposite cord; a zig-4::gfp reporter fusion is expressed in the PVT, ASK, BAG, and M2 neurons, with expression also seen during the L1 stage in pharyngeal mesoderm and ectoderm.