The National Institute of Diabetes & Digestive & Kidney Diseases

The development of a viable, fertile multicellular organism involves the temporal and spatial coordination of many cell divisions. My laboratory is interested in understanding how these cell divisions are regulated so that cells are born at the right place and time during development. The components that regulate and drive the cell cycle have been identified by genetic, biochemical, and molecular approaches in a number of different model systems. While we have a good understanding of how these components function biochemically, we have a poor understanding of how these components are regulated during development to generate multicellular organisms. Our studies focus on evolutionarily-conserved cell cycle genes in the model organism Caenorhabditis elegans. C. elegans is a hermaphroditic soil nematode for which its entire cell lineage is known. From this invariant developmental blueprint, it is obvious that regulatory mechanisms must exist to regulate cell division so that cells divide at different rates and times during development. Because the entire cell lineage is known, we can determine, at the single cell level, the specific developmental requirement of a given cell cycle gene.

We currently use forward and reverse genetics to determine the role of numerous cell cycle regulatory genes that have been conserved throughout evolution. These studies have revealed that many of these genes function early in development, leading us to focus on events just prior to fertilization and events immediately following fertilization. Oocytes and early embryos are large in size and easy to visualize in live animals. Thus we have been able to characterize the phenotypes associated with loss of expression of these conserved genes Click here for details of our ongoing projects.

emb-1 encodes the APC16 subunit of the Caenorhabditis elegansAnaphase-Promoting Complex Shakes DC, Allen AK, Albert KM, Golden A Genetics (189):549-560, 2011.

Protein phosphatase 5 is a negative regulator of separase function during cortical granule exocytosis in C. elegans. Richie CT, Bembenek JN, Chestnut B, Furuta T, Schumacher JM, Wallenfang M, Golden A. J Cell Sci (124):2903-13, 2011.

Functional redundancy of paralogs of an anaphase promoting complex/cyclosome subunit in Caenorhabditis elegans meiosis. Stein KK, Nesmith JE, Ross BD, Golden A. Genetics (186):1285-93, 2010.

Inactivation of the C. elegans lipin homolog leads to ER disorganization and to defects in the breakdown and reassembly of the nuclear envelope. Golden A, Liu J, Cohen-Fix O. J Cell Sci. (122):1970-8, 2009.

Multiple ERK substrates execute single biological processes in Caenorhabditis elegans germ-line development. Arur S, Ohmachi M, Nayak S, Hayes M, Miranda A, Hay A, Golden A, Schedl T. Proc Natl Acad Sci U S A. (106): 4776-81, 2009.

Stein KK, Davis ES, Hays T, Golden A Components of the spindle assembly checkpoint regulate the anaphase-promoting complex during meiosis in Caenorhabditis elegans. Genetics(175): 107-23, 2007. [Full Text/Abstract]

Bembenek JN, Richie CT, Squirrell JM, Campbell JM, Eliceiri KW, Poteryaev D, Spang A, Golden A, White JG Cortical granule exocytosis in C. elegans is regulated by cell cycle components including separase. Development(134): 3837-3848, 2007. [Full Text/Abstract]

Golden A, O''Connell KF Silence is golden: combining RNAi and live cell imaging to study cell cycle regulatory genes during Caenorhabditis elegans development. Methods(41): 190-7, 2007. [Full Text/Abstract]

Burrows AE, Sceurman BK, Kosinski ME, Richie CT, Sadler PL, Schumacher JM, Golden A The C. elegans Myt1 ortholog is required for the proper timing of oocyte maturation. Development (133): 697-709, 2006. [Full Text/Abstract]

Richie CT, Golden A Chromosome segregation: Aurora B gets Tousled. Curr Biol (15): R379-82, 2005. [Full Text/Abstract]

Shakes DC Sadler PL Schumacher JM Abdolrasulnia M Golden A Developmental defects observed in hypomorphic anaphase-promoting complex mutants are linked to cell cycle abnormalities. Development (130): 1605-20, 2003. [Full Text/Abstract]

Golden A Cohen-Fix O Getting (chromosomes) loaded--a new role for timeless. Dev Cell (5): 7-9, 2003. [Full Text/Abstract]

Ashcroft N Golden A CDC-25.1 regulates germline proliferation in Caenorhabditis elegans. Genesis (33): 1-7, 2002. [Full Text/Abstract]

Davis ES Wille L Chestnut BA Sadler PL Shakes DC Golden A Multiple subunits of the Caenorhabditis elegans anaphase-promoting complex are required for chromosome segregation during meiosis I. Genetics (160): 805-13, 2002. [Full Text/Abstract]

Morton DG Shakes DC Nugent S Dichoso D Wang W Golden A Kemphues KJ The Caenorhabditis elegans par-5 gene encodes a 14-3-3 protein required for cellular asymmetry in the early embryo. Dev Biol (241): 47-58, 2002. [Full Text/Abstract]

Chase D Golden A Heidecker G Ferris DK Caenorhabditis elegans contains a third polo-like kinase gene. DNA Seq (11): 327-34, 2000. [Full Text/Abstract]

Golden A Cytoplasmic flow and the establishment of polarity in C. elegans 1-cell embryos. Curr Opin Genet Dev (10): 414-20, 2000. [Full Text/Abstract]

Golden A Sadler PL Wallenfang MR Schumacher JM Hamill DR Bates G Bowerman B Seydoux G Shakes DC Metaphase to anaphase (mat) transition-defective mutants in Caenorhabditis elegans. J Cell Biol (151): 1469-82, 2000. [Full Text/Abstract]

Chase D Serafinas C Ashcroft N Kosinski M Longo D Ferris DK Golden A The polo-like kinase PLK-1 is required for nuclear envelope breakdown and the completion of meiosis in Caenorhabditis elegans. Genesis (26): 26-41, 2000. [Full Text/Abstract]

Wilson MA Hoch RV Ashcroft NR Kosinski ME Golden A A Caenorhabditis elegans wee1 homolog is expressed in a temporally and spatially restricted pattern during embryonic development. Biochim Biophys Acta (1445): 99-109, 1999. [Full Text/Abstract]

Ashcroft NR Srayko M Kosinski ME Mains PE Golden A RNA-Mediated interference of a cdc25 homolog in Caenorhabditis elegans results in defects in the embryonic cortical membrane, meiosis, and mitosis. Dev Biol (206): 15-32, 1999. [Full Text/Abstract]

Schumacher JM Ashcroft N Donovan PJ Golden A A highly conserved centrosomal kinase, AIR-1, is required for accurate cell cycle progression and segregation of developmental factors in Caenorhabditis elegans embryos. Development (125): 4391-402, 1998. [Full Text/Abstract]

Schumacher JM Golden A Donovan PJ AIR-2: An Aurora/Ipl1-related protein kinase associated with chromosomes and midbody microtubules is required for polar body extrusion and cytokinesis in Caenorhabditis elegans embryos. J Cell Biol (143): 1635-46, 1998. [Full Text/Abstract]

Ashcroft NR Kosinski ME Wickramasinghe D Donovan PJ Golden A The four cdc25 genes from the nematode Caenorhabditis elegans. Gene (214): 59-66, 1998. [Full Text/Abstract]

Sternberg PW Yoon CH Lee J Jongeward GD Kayne PS Katz WS Lesa G Liu J Golden A Huang LS et al Molecular genetics of proto-oncogenes and candidate tumor suppressors in Caenorhabditis elegans. Cold Spring Harb Symp Quant Biol (59): 155-63, 1994. [Full Text/Abstract]

Han M Golden A Han Y Sternberg PW C. elegans lin-45 raf gene participates in let-60 ras-stimulated vulval differentiation. Nature (363): 133-40, 1993. [Full Text/Abstract]

Sternberg PW Golden A Han M Role of a raf proto-oncogene during Caenorhabditis elegans vulval development. Philos Trans R Soc Lond B Biol Sci (340): 259-65, 1993. [Full Text/Abstract]