The multivulval phenotype is presumably due to INTRA not being degraded by the proteasome, resulting in an increase in Notch signaling (Mango 1991; Westlund 1997)

The multivulval phenotype is presumably due to INTRA not being degraded by the proteasome, resulting in an increase in Notch signaling (Mango 1991; Westlund 1997). regulator of the Notch-signaling pathway, while the other functions on one of the two major redundant genetic pathways downstream of GLP-1/Notch signaling. We propose a model in which the proteasome degrades proteins that are necessary for proliferation as cells switch from proliferation to meiotic access. THE production of gametes is an essential process in any sexually reproducing species. In most of these species, proliferation of germ-line stem cells is needed first to Pyrotinib Racemate generate the germ-line tissue and then to maintain a supply from which future gametes can be created. If germ-line stem cell proliferation does not keep pace with gamete production, the population of stem cells will be depleted, resulting in sterility. Conversely, an increase in self-renewing proliferation of the germ-line stem cells at the expense of gamete production can also result in sterility, as well as tumor formation. With the large numbers of gametes that are created over the life of some animals, it is imperative that the balance between proliferation and differentiation be fine-tuned; a slight shift in this balance will be amplified over time and greatly reduce the reproductive fitness of the animal. Much of our understanding of how the balance between germ-line proliferation and differentiation is usually controlled comes from study of classic genetic model organisms such as Drosophila and 1994; Tax 1994). The conversation between ligand and receptor activates GLP-1/Notch signaling, which presumably culminates in the expression of genes necessary for proliferation and the inhibition of genes involved in meiotic entry. As germ cells move proximally, away from the influence of the DTC, the level of GLP-1/Notch signaling is usually thought to diminish, presumably allowing for the gene activity profile to switch, resulting in cells entering into meiotic prophase and eventually forming fully differentiated gametes. Numerous genetic screens for mutants that disrupt the balance between proliferation and differentiation in the germ collection, as well as phenotypic analysis of preexisting mutants, have recognized many genes that control the balance between proliferation and differentiation (Hansen and Schedl 2006; Kimble and Crittenden 2007); most of these genes either modulate GLP-1/Notch signaling or are regulated by GLP-1/Notch signaling. Genetic epistasis analysis of these mutants has resulted in a genetic model (Physique 1A), which has been supported by substantial biochemical evidence. In this model, GLP-1/Notch signaling promotes the activities of two nearly identical proteins, FBF-1 and FBF-2, which are homologous to Drosophila Pumilio (Crittenden 2002; Lamont 2004). FBF-1 and FBF-2 then inhibit the activities of two major genetic pathways that function redundantly to inhibit proliferation and/or promote meiotic access (Kadyk and Kimble Pyrotinib Racemate 1998; Crittenden 2002; Eckmann 2004); we will refer to these two pathways as the and pathways on the basis of the founding genes of these two pathways (Francis 1995b; Kadyk and Kimble 1998). When germ cells are close to the DTC, GLP-1/Notch signaling is usually active and the activities of the and pathways are inhibited. As germ cells move away from the DTC and GLP-1/Notch signaling is usually reduced, the activities of the genes in the and pathways increase, resulting in cells entering into meiotic prophase. The and pathways function redundantly: if a gene in only one of the pathways is usually mutated, the balance between proliferation and differentiation is very similar to wild type (Francis 1995b; Kadyk and Kimble 1998). Rabbit polyclonal to ADAM20 However, if the activities of both pathways are eliminated by mutating a gene in each of the two pathways, the balance is usually shifted toward proliferation and a germ-line tumor results (Kadyk and Kimble 1998; Eckmann 2004; Hansen 2004b). Pyrotinib Racemate On the basis of the molecular identities of the genes Pyrotinib Racemate in the and pathways and biochemical analysis, all known components of these pathways likely regulate mRNA metabolism. GLD-1 is usually a KH-domain-containing protein that binds to target mRNAs and inhibits translation (Jones and Schedl 1995; Jan 1999;.