The heterochronic genes lin-4, lin-14, lin-28, and lin-29 specify the timing of lateral hypodermal seam cell terminal differentiation in Caenorhabditis elegans. We devised a screen to identify additional genes involved in this developmental timing mechanism based on identification of mutants that exhibit temporal misexpression from the col-19 promoter, a downstream target of the heterochronic g...

Wnt proteins are intercellular signals that regulate various aspects of animal development. In Caenorhabditis elegans, mutations in lin-17, a Frizzled-class Wnt receptor, and in lin-18 affect cell fate patterning in the P7.p vulval lineage. We found that lin-18 encodes a member of the Ryk/Derailed family of tyrosine kinase-related receptors, recently found to function as Wnt receptors. Members ...

Mutations in the C. elegans gene lin-44 lead to reversals in the polarity of certain asymmetric cell divisions. We have discovered that lin-44 is a member of the Wnt family of genes, which encode secretory glycoproteins implicated in intercellular signaling. Both in situ hybridization experiments using lin-44 transcripts and experiments using reporter constructs designed to mimic patterns of li...

The Caenorhabditis elegans heterochronic gene pathway, which consists of a set of regulatory genes, plays an important regulatory role in the timing of stage-specific cell lineage development in nematodes. Research into the heterochronic gene pathway gave rise to landmark microRNA (miRNA) studies and showed that these genes are important in stem cell and cancer biology; however, their functions...

X.S. Lin’s original definition of twisted Alexander knot polynomial is generalized for arbitrary finitely presented groups. J. Cha’s fibering obstruction theorem is generalized. The group of a nontrivial virtual knot shown by L. Kauffman to have trivial Jones polynomial is seen also to have a faithful representation that yields a trivial twisted Alexander polynomial.

ownload lin-dependent kinases (CDK) are key positive regulators of cell cycle progression and attractive targets ology. SCH 727965 inhibits CDK2, CDK5, CDK1, and CDK9 activity in vitro with IC50 values of 1, 1, 3, nmol/L, respectively. SCH 727965 was selected as a clinical candidate using a functional screen in vivo tegrated both efficacy and safety parameters. Comparedwith flavopiridol, SCH 72...

MicroRNAs (miRNAs) are full of surprises. The more we study these ~22-nucleotide non-coding RNAs, the more we realize how little is understood about this mode of gene regulation. 1 Case in point: lin-4, the founding member of the miRNA superfamily discovered over 20 years ago. Thousands of miRNAs have since been discovered in plant, animal, and viral genomes. They direct important cellular proc...

The Caenorhabditis elegans LIN-26 protein is required to specify and/or maintain the fates of all non-neuronal ectodermal cells. Here we show that lin-26 is expressed until the somatic gonad primordium stage in all cells of the somatic gonad, except in distal tip cells, and later in all uterine cells. To determine if lin-26 functions in the somatic gonad, we have generated gonad-specific lin-26...

The single C. elegans member of the retinoblastoma gene family, lin-35 Rb, was originally identified as a synthetic Multivulva (synMuv) gene [1]. These genes form two redundant classes, A and B, that repress ectopic vulval cell fate induction. Recently, we demonstrated that lin-35 Rb also acts as a negative regulator of G(1) progression and likely is the major target of cyd-1 Cyclin D and cdk-4...