Disease relevance of glp-1

• Here we analyse an unusual allele of glp-1, glp-1(q35), which displays a semidominant multivulva phenotype (Muv), as well as the typical recessive, loss-of-function Glp phenotypes (sterility and embryonic lethality) [1].

High impact information on glp-1

• The maternal genes apx-1 and glp-1 and establishment of dorsal-ventral polarity in the early C. elegans embryo [2].
• By contrast, glp-1 mRNA is present in all blastomeres until the 8-cell stage [3].
• In one model, we propose that the AC sends an intercellular signal intended to interact with the lin-12 product in somatic gonadal cells; when lin-12 activity is absent, the signal interacts instead with the related glp-1 product in germline [4].
• The glp-1 and lin-12 genes mediate several cell interactions during C. elegans development [5].
• Mutations in glp-1 cause germ cells that would normally divide mitotically to enter meiosis [6].

Biological context of glp-1

• The glp-1 and lin-12 genes encode homologous transmembrane proteins that may act as receptors for cell interactions during development [1].
• The glp-1 product is required for induction of germ-line proliferation and for embryogenesis [1].
• These include the fog-1 temperature sensitive period, which coincides in each sex with first entry into meiosis, and the phenotype of a fog-1; glp-1 double mutant [7].
• The glp-1 gene is required for embryonic induction and continued germline proliferation; lin-12 is required for cells of equal developmental potential to adopt different fates [8].
• glp-1 is required in the germ line for regulation of the decision between mitosis and meiosis in C. elegans [6].

Anatomical context of glp-1

• The glp-1 gene functions in two inductive cellular interactions and in development of the embryonic hypodermis of C. elegans [9].
• In the light of current ideas about the molecular nature of the glp-1 and suppressor gene products, we propose an interaction between the glp-1 protein and components of the extracellular matrix and speculate that this interaction may impose spatial constraints on the decision between mitosis and meiosis in the germline [9].
• The validity of the method was confirmed through results with control genes whose expression patterns have been reported; glp-1 in very early embryos, myo-2 in pharyngeal muscle and unc-54 in body wall muscle [10].
• The glp-1 gene is essential for two cell interactions that control cell fate in Caenorhabditis elegans: induction of anterior pharynx in the embryo and induction of mitotic proliferation in the germ line [11].
• The glp-1 gene mediates a signal that promotes mitosis and the genes of the sex determination pathway mediate a signal that determines if germ cells will develop as sperm or oocytes [12].

Associations of glp-1 with chemical compounds

• Here, we report that sel-8 is essential for lin-12- and glp-1-mediated signaling, and that SEL-8 is a glutamine-rich nuclear protein [13].

Physical interactions of glp-1

• Suppressors of a lin-12 hypomorph define genes that interact with both lin-12 and glp-1 in Caenorhabditis elegans [14].

Regulatory relationships of glp-1

• Unexpectedly, we find that glp-1 RNA is also expressed in larval somatic tissues and that lin-12 RNA is abundant in early embryos [5].

Other interactions of glp-1

• Genetic studies indicate that the lin-12 and glp-1 proteins act as receptors in specific developmental cell interactions and that their functions are partially redundant. lin-12 glp-1 double mutants display certain embryonic defects not found in either single mutant [15].
• ABa and ABp, the other two sisters in a 4-cell embryo, are influenced to develop differently by cell signaling events that require the two genes apx-1 and glp-1 [16].
• In the absence of tbx-2 function, ABa-derived cells initiate development normally: they receive glp-1/Notch signaling cues, activate the T-box gene TBX-38 and express the organ selector gene PHA-4/FoxA [17].
• TBX-2 is expressed in ABa descendants and depends on activation by pha-4 and repression by components of glp-1/Notch signaling [17].
• The Caenorhabditis elegans sel-1 gene, a negative regulator of lin-12 and glp-1, encodes a predicted extracellular protein [18].

References