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The C. elegans TPR Containing Protein, TRD-1, Regulates Cell Fate Choice in the Developing Germ Line and Epidermis.

Hughes S, Wilkinson H, Gilbert SP, Kishida M, Ding SS, Woollard A - PLoS ONE (2014)

Bottom Line: In the germline, stem cells adopt one of three possible fates: mitotic cell cycle, or gamete formation via meiosis, producing either sperm or oocytes.In the epidermis, the stem cell-like seam cells divide asymmetrically, with the daughters taking on either a proliferative (seam) or differentiated (hypodermal or neuronal) fate.We show that trd-1(RNAi) and mutant animals have fewer seam cells as a result of inappropriate differentiation towards the hypodermal fate.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, University of Oxford, Oxford, United Kingdom.

ABSTRACT
Correct cell fate choice is crucial in development. In post-embryonic development of the hermaphroditic Caenorhabitis elegans, distinct cell fates must be adopted in two diverse tissues. In the germline, stem cells adopt one of three possible fates: mitotic cell cycle, or gamete formation via meiosis, producing either sperm or oocytes. In the epidermis, the stem cell-like seam cells divide asymmetrically, with the daughters taking on either a proliferative (seam) or differentiated (hypodermal or neuronal) fate. We have isolated a novel conserved C. elegans tetratricopeptide repeat containing protein, TRD-1, which is essential for cell fate determination in both the germline and the developing epidermis and has homologs in other species, including humans (TTC27). We show that trd-1(RNAi) and mutant animals have fewer seam cells as a result of inappropriate differentiation towards the hypodermal fate. In the germline, trd-1 RNAi results in a strong masculinization phenotype, as well as defects in the mitosis to meiosis switch. Our data suggests that trd-1 acts downstream of tra-2 but upstream of fem-3 in the germline sex determination pathway, and exhibits a constellation of phenotypes in common with other Mog (masculinization of germline) mutants. Thus, trd-1 is a new player in both the somatic and germline cell fate determination machinery, suggestive of a novel molecular connection between the development of these two diverse tissues.

No MeSH data available.


Related in: MedlinePlus

Genetic regulation of germline sex determination.The pathway consists of a cascade of regulatory interactions driving sexual fate. Essentially, fem-1, -2 and -3 together with fog-1 and fog-3 promote spermatogenesis. To allow hermaphrodite animals to switch to oocyte production at the late L4 stage, tra-2 is repressed by the action of FOG-2 and GLD-1. fem-3 is repressed at the level of mRNA by multiple factors. Thus, regulation of the balance of TRA-2 and FEM-3 levels allows the timely transition from sperm to oocyte production, in order to generate fully fertile hermaphrodites. Factors that promote male and female fates are highlighted in blue and red, respectively. Adapted from Kimble and Crittenden [14] and Rybarska et al.[41].
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pone-0114998-g001: Genetic regulation of germline sex determination.The pathway consists of a cascade of regulatory interactions driving sexual fate. Essentially, fem-1, -2 and -3 together with fog-1 and fog-3 promote spermatogenesis. To allow hermaphrodite animals to switch to oocyte production at the late L4 stage, tra-2 is repressed by the action of FOG-2 and GLD-1. fem-3 is repressed at the level of mRNA by multiple factors. Thus, regulation of the balance of TRA-2 and FEM-3 levels allows the timely transition from sperm to oocyte production, in order to generate fully fertile hermaphrodites. Factors that promote male and female fates are highlighted in blue and red, respectively. Adapted from Kimble and Crittenden [14] and Rybarska et al.[41].

Mentions: Hermaphrodites initially produce sperm, switching to oocyte production in late L4 for the remainder of their lives [9], [10]. The switch from spermatogenesis to oogenesis is dependent upon many putative RNA regulatory proteins including FBF-1, FBF-2, NOS-3, GLD-1, 2 and 3, and the MOG family of proteins, as well as the terminal regulators FOG-1 and FOG-3 (Fig. 1) [11]–[15]. Post-transcriptional regulation of germline sex determination makes sense in hermaphrodite animals, where feminizing signals from somatic tissue (set up by the chromosomal X:A ratio) must be transiently over-ridden. Important nodes in the germline sex determination pathway include the masculinizing FEM-3 and the feminizing TRA-2, both of which have been shown to be major targets of the RNA regulatory machinery [13], [16]–[18]. Thus the balance between TRA-2 and FEM-3 activities is an important determinant of whether a germ cell differentiates as sperm or oocyte [19]. This is supported by experimental evidence showing that fem-3(gf) single mutants produce only sperm, whereas tra-2(gf) single mutants produce only oocytes, whereas the double mutant develops as a fertile hermaphrodite [20]–[22]. Thus, the relative activity of FEM-3 and TRA-2 is the crucial driver of gamete fate. Intriguingly, some of the genes involved in the switch between spermatogenesis and oogenesis in the proximal germline also control the “upstream” decision between mitosis and meiosis in the distal germline, suggesting a possible evolutionary relationship of these regulatory pathways [11].


The C. elegans TPR Containing Protein, TRD-1, Regulates Cell Fate Choice in the Developing Germ Line and Epidermis.

Hughes S, Wilkinson H, Gilbert SP, Kishida M, Ding SS, Woollard A - PLoS ONE (2014)

Genetic regulation of germline sex determination.The pathway consists of a cascade of regulatory interactions driving sexual fate. Essentially, fem-1, -2 and -3 together with fog-1 and fog-3 promote spermatogenesis. To allow hermaphrodite animals to switch to oocyte production at the late L4 stage, tra-2 is repressed by the action of FOG-2 and GLD-1. fem-3 is repressed at the level of mRNA by multiple factors. Thus, regulation of the balance of TRA-2 and FEM-3 levels allows the timely transition from sperm to oocyte production, in order to generate fully fertile hermaphrodites. Factors that promote male and female fates are highlighted in blue and red, respectively. Adapted from Kimble and Crittenden [14] and Rybarska et al.[41].
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4262444&req=5

pone-0114998-g001: Genetic regulation of germline sex determination.The pathway consists of a cascade of regulatory interactions driving sexual fate. Essentially, fem-1, -2 and -3 together with fog-1 and fog-3 promote spermatogenesis. To allow hermaphrodite animals to switch to oocyte production at the late L4 stage, tra-2 is repressed by the action of FOG-2 and GLD-1. fem-3 is repressed at the level of mRNA by multiple factors. Thus, regulation of the balance of TRA-2 and FEM-3 levels allows the timely transition from sperm to oocyte production, in order to generate fully fertile hermaphrodites. Factors that promote male and female fates are highlighted in blue and red, respectively. Adapted from Kimble and Crittenden [14] and Rybarska et al.[41].
Mentions: Hermaphrodites initially produce sperm, switching to oocyte production in late L4 for the remainder of their lives [9], [10]. The switch from spermatogenesis to oogenesis is dependent upon many putative RNA regulatory proteins including FBF-1, FBF-2, NOS-3, GLD-1, 2 and 3, and the MOG family of proteins, as well as the terminal regulators FOG-1 and FOG-3 (Fig. 1) [11]–[15]. Post-transcriptional regulation of germline sex determination makes sense in hermaphrodite animals, where feminizing signals from somatic tissue (set up by the chromosomal X:A ratio) must be transiently over-ridden. Important nodes in the germline sex determination pathway include the masculinizing FEM-3 and the feminizing TRA-2, both of which have been shown to be major targets of the RNA regulatory machinery [13], [16]–[18]. Thus the balance between TRA-2 and FEM-3 activities is an important determinant of whether a germ cell differentiates as sperm or oocyte [19]. This is supported by experimental evidence showing that fem-3(gf) single mutants produce only sperm, whereas tra-2(gf) single mutants produce only oocytes, whereas the double mutant develops as a fertile hermaphrodite [20]–[22]. Thus, the relative activity of FEM-3 and TRA-2 is the crucial driver of gamete fate. Intriguingly, some of the genes involved in the switch between spermatogenesis and oogenesis in the proximal germline also control the “upstream” decision between mitosis and meiosis in the distal germline, suggesting a possible evolutionary relationship of these regulatory pathways [11].

Bottom Line: In the germline, stem cells adopt one of three possible fates: mitotic cell cycle, or gamete formation via meiosis, producing either sperm or oocytes.In the epidermis, the stem cell-like seam cells divide asymmetrically, with the daughters taking on either a proliferative (seam) or differentiated (hypodermal or neuronal) fate.We show that trd-1(RNAi) and mutant animals have fewer seam cells as a result of inappropriate differentiation towards the hypodermal fate.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, University of Oxford, Oxford, United Kingdom.

ABSTRACT
Correct cell fate choice is crucial in development. In post-embryonic development of the hermaphroditic Caenorhabitis elegans, distinct cell fates must be adopted in two diverse tissues. In the germline, stem cells adopt one of three possible fates: mitotic cell cycle, or gamete formation via meiosis, producing either sperm or oocytes. In the epidermis, the stem cell-like seam cells divide asymmetrically, with the daughters taking on either a proliferative (seam) or differentiated (hypodermal or neuronal) fate. We have isolated a novel conserved C. elegans tetratricopeptide repeat containing protein, TRD-1, which is essential for cell fate determination in both the germline and the developing epidermis and has homologs in other species, including humans (TTC27). We show that trd-1(RNAi) and mutant animals have fewer seam cells as a result of inappropriate differentiation towards the hypodermal fate. In the germline, trd-1 RNAi results in a strong masculinization phenotype, as well as defects in the mitosis to meiosis switch. Our data suggests that trd-1 acts downstream of tra-2 but upstream of fem-3 in the germline sex determination pathway, and exhibits a constellation of phenotypes in common with other Mog (masculinization of germline) mutants. Thus, trd-1 is a new player in both the somatic and germline cell fate determination machinery, suggestive of a novel molecular connection between the development of these two diverse tissues.

No MeSH data available.


Related in: MedlinePlus