Cell cycle-dependent sequencing of cell fate decisions in Caenorhabditis elegans vulva precursor cells.

In Caenorhabditis elegans, the fates of the six multipotent vulva precursor cells (VPCs) are specified by extracellular signals. One VPC expresses the primary (1 degrees ) fate in response to a Ras-mediated inductive signal from the gonad. The two VPCs flanking the 1 degrees cell each express secondary (2 degrees ) fates in response to lin-12-mediated lateral signaling. The remaining three VPCs each adopt the non-vulval tertiary (3 degrees ) fate. Here I describe experiments examining how the selection of these vulval fates is affected by cell cycle arrest and cell cycle-restricted lin-12 activity. The results suggest that lin-12 participates in two developmental decisions separable by cell cycle phase: lin-12 must act prior to the end of VPC S phase to influence a 1 degrees versus 2 degrees cell fate choice, but must act after VPC S phase to influence a 3 degrees versus 2 degrees cell fate choice. Coupling developmental decisions to cell cycle transitions may provide a mechanism for prioritizing or ordering choices of cell fates for multipotential cells.

[1]  I. Greenwald,et al.  LIN-12/Notch signaling: lessons from worms and flies. , 1998, Genes & development.

[2]  C. Lehner,et al.  Cell fate specification by even-skipped expression in the Drosophila nervous system is coupled to cell cycle progression. , 1995, Development.

[3]  V. Ambros,et al.  Heterochronic Genes Control Cell Cycle Progress and Developmental Competence of C. elegans Vulva Precursor Cells , 1996, Cell.

[4]  J. Sulston,et al.  Post-embryonic cell lineages of the nematode, Caenorhabditis elegans. , 1977, Developmental biology.

[5]  E. Hedgecock,et al.  Limitation of the size of the vulval primordium of Caenorhabditis elegans by lin-15 expression in surrounding hypodermis , 1990, Nature.

[6]  C. Kenyon A perfect vulva every time: Gradients and signaling cascades in C. elegans , 1995, Cell.

[7]  S. Zipursky,et al.  Cell cycle progression in the developing Drosophila eye: roughex encodes a novel protein required for the establishment of G1 , 1994, Cell.

[8]  Y. Ohshima,et al.  Mosaic analysis of the let-23 gene function in vulval induction of Caenorhabditis elegans. , 1995, Development.

[9]  Paul W. Sternberg,et al.  The combined action of two intercellular signaling pathways specifies three cell fates during vulval induction in C. elegans , 1989, Cell.

[10]  I. Greenwald,et al.  LIN-12 protein expression and localization during vulval development in C. elegans. , 1998, Development.

[11]  J. Slack From Egg to Embryo , 1983 .

[12]  V. Hartenstein,et al.  Sensillum development in the absence of cell division: the sensillum phenotype of the Drosophila mutant string. , 1990, Developmental biology.

[13]  P. Sternberg,et al.  let-60, a gene that specifies cell fates during C. elegans vulval induction, encodes a ras protein , 1990, Cell.

[14]  H. Horvitz,et al.  The lin-12 locus specifies cell fates in caenorhabditis elegans , 1983, Cell.

[15]  S. Mcconnell,et al.  Cell cycle dependence of laminar determination in developing neocortex , 1991 .

[16]  G. Struhl,et al.  Intrinsic activity of the lin-12 and Notch intracellular domains in vivo , 1993, Cell.

[17]  H. Horvitz,et al.  The Caenorhabditis elegans locus lin-15, a negative regulator of a tyrosine kinase signaling pathway, encodes two different proteins. , 1994, Genetics.

[18]  H. Horvitz,et al.  Heterochronic mutants of the nematode Caenorhabditis elegans. , 1984, Science.

[19]  R. Gomer,et al.  Cell-autonomous determination of cell-type choice in Dictyostelium development by cell-cycle phase. , 1987, Science.

[20]  H. Wilkinson,et al.  Spatial and temporal patterns of lin-12 expression during C. elegans hermaphrodite development. , 1995, Genetics.

[21]  J. Sulston,et al.  Some Observations On Moulting in Caenorhabditis Elegans , 1978 .

[22]  I. Greenwald lin-12, a nematode homeotic gene, is homologous to a set of mammalian proteins that includes epidermal growth factor , 1985, Cell.

[23]  V. Ambros,et al.  Developmental regulation of a cyclin-dependent kinase inhibitor controls postembryonic cell cycle progression in Caenorhabditis elegans. , 1998, Development.

[24]  P. O’Farrell,et al.  The three postblastoderm cell cycles of Drosophila embryogenesis are regulated in G2 by string , 1990, Cell.

[25]  Stuart K. Kim,et al.  Sequential signalling during Caenorhabditis elegans vulval induction , 1995 .

[26]  J. Bettinger,et al.  Stage-specific accumulation of the terminal differentiation factor LIN-29 during Caenorhabditis elegans development. , 1996, Development.

[27]  Paul W. Sternberg,et al.  Pattern formation during vulval development in C. elegans , 1986, Cell.

[28]  R. Grainger,et al.  Changes in neural and lens competence in Xenopus ectoderm: evidence for an autonomous developmental timer. , 1991, Development.

[29]  Paul W. Sternberg,et al.  Lateral inhibition during vulval induction in Caenorhabditis elegans , 1988, Nature.

[30]  R. Burdine,et al.  EGL-17(FGF) expression coordinates the attraction of the migrating sex myoblasts with vulval induction in C. elegans. , 1998, Development.

[31]  G. Struhl,et al.  Nuclear Access and Action of Notch In Vivo , 1998, Cell.

[32]  G. Wu,et al.  sel-10, a negative regulator of lin-12 activity in Caenorhabditis elegans, encodes a member of the CDC4 family of proteins. , 1997, Genes & development.

[33]  Hilla Peretz,et al.  Ju n 20 03 Schrödinger ’ s Cat : The rules of engagement , 2003 .

[34]  W. Harris,et al.  Neuronal determination without cell division in xenopus embryos , 1991, Neuron.

[35]  H. Horvitz,et al.  lin-35 and lin-53, Two Genes that Antagonize a C. elegans Ras Pathway, Encode Proteins Similar to Rb and Its Binding Protein RbAp48 , 1998, Cell.

[36]  R. Weinberg,et al.  The retinoblastoma protein and cell cycle control , 1995, Cell.

[37]  W. Wood The Nematode Caenorhabditis elegans , 1988 .

[38]  P. Sternberg,et al.  The lin-15 locus encodes two negative regulators of Caenorhabditis elegans vulval development. , 1994, Molecular biology of the cell.

[39]  H. Horvitz,et al.  A genetic pathway for the specification of the vulval cell lineages of Caenorhabditis elegans , 1987, Nature.

[40]  Paul W. Sternberg,et al.  The gene lin-3 encodes an inductive signal for vulval development in C. elegans , 1992, Nature.

[41]  S. Brenner The genetics of Caenorhabditis elegans. , 1974, Genetics.

[42]  H. Horvitz,et al.  The Caenorhabditis elegans gene lin-1 encodes an ETS-domain protein and defines a branch of the vulval induction pathway. , 1995, Genes & development.

[43]  J Kimble,et al.  Alterations in cell lineage following laser ablation of cells in the somatic gonad of Caenorhabditis elegans. , 1981, Developmental biology.