The signal transducer CD24 suppresses the germ cell program and promotes an ectodermal rather than mesodermal cell fate in embryonal carcinomas

The germ cell lineage in mammals is induced by the stimulation of pluripotent epiblast cells with signaling molecules. Previous studies have suggested that the germ cell differentiation competence or responsiveness of epiblast cells to signaling molecules is established and maintained in epiblast cells of a specific differentiation state. However, the molecular mechanism underlying this process has not been well defined. Here, using the differentiation model of epiblast stem cells (EpiSCs), we have shown that two defined EpiSC lines have robust germ cell differentiation competence. However, another defined EpiSC line has no competence. By evaluating the molecular basis of EpiSCs with distinct germ cell differentiation competence, we identified YAP/YAP1/YAP65, an intracellular mediator of the Hippo signaling pathway, as a critical mediator for establishing germ cell induction. Strikingly, deletion of YAP severely affected responsiveness to inductive stimuli, leading to a defect in WNT target activation and germ cell differentiation. In conclusion, we propose that the Hippo/YAP signaling pathway creates a potential for germ cell fate induction via mesodermal WNT signaling in pluripotent epiblast cells.

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Differential regulation of gastrulation and neuroectodermal gene expression by Snail in the Drosophila embryo

Development ◽

10.1242/dev.124.19.3683 ◽

1997 ◽

Vol 124 (19) ◽

pp. 3683-3691 ◽

Cited By ~ 4

Author(s):

K. Hemavathy ◽

X. Meng ◽

Y.T. Ip

Keyword(s):

Cell Fate ◽

Target Genes ◽

Expression Patterns ◽

Cell Movement ◽

Drosophila Embryo ◽

Intermediate Phenotype ◽

Gene Products ◽

Mesodermal Cell ◽

Possible Cause ◽

Mesodermal Lineage

The initiation of mesoderm differentiation in the Drosophila embryo requires the gene products of twist and snail. In either mutant, the ventral cell invagination during gastrulation is blocked and no mesoderm-derived tissue is formed. One of the functions of Snail is to repress neuroectodermal genes and restrict their expressions to the lateral regions. The derepression of the neuroectodermal genes into the ventral region in snail mutant is a possible cause of defects in gastrulation and in mesoderm differentiation. To investigate such possibility, we analysed a series of snail mutant alleles. We found that different neuroectodermal genes respond differently in various snail mutant background. Due to the differential response of target genes, one of the mutant alleles, V2, that has reduced Snail function showed an intermediate phenotype. In V2 embryos, neuroectodermal genes, such as single-minded and rhomboid, are derepressed while ventral invagination proceeds normally. However, the differentiation of these invaginated cells into mesodermal lineage is disrupted. The results suggest that the establishment of mesodermal cell fate requires the proper restriction of neuroectodermal genes, while the ventral cell movement is independent of the expression patterns of these genes. Together with the data showing that the expression of some ventral genes disappear in snail mutants, we propose that Snail may repress or activate another set of target genes that are required specifically for gastrulation.

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Genetic control of programmed cell death in the Caenorhabditis elegans hermaphrodite germline

Development ◽

10.1242/dev.126.5.1011 ◽

1999 ◽

Vol 126 (5) ◽

pp. 1011-1022 ◽

Cited By ~ 8

Author(s):

T.L. Gumienny ◽

E. Lambie ◽

E. Hartwieg ◽

H.R. Horvitz ◽

M.O. Hengartner

Keyword(s):

Cell Death ◽

Caenorhabditis Elegans ◽

Germ Cell ◽

Somatic Cell ◽

Cell Fate ◽

Germ Cells ◽

Mapk Pathway ◽

Apoptotic Cell ◽

C Elegans ◽

Pathway Activation

Development of the nematode Caenorhabditis elegans is highly reproducible and the fate of every somatic cell has been reported. We describe here a previously uncharacterized cell fate in C. elegans: we show that germ cells, which in hermaphrodites can differentiate into sperm and oocytes, also undergo apoptotic cell death. In adult hermaphrodites, over 300 germ cells die, using the same apoptotic execution machinery (ced-3, ced-4 and ced-9) as the previously described 131 somatic cell deaths. However, this machinery is activated by a distinct pathway, as loss of egl-1 function, which inhibits somatic cell death, does not affect germ cell apoptosis. Germ cell death requires ras/MAPK pathway activation and is used to maintain germline homeostasis. We suggest that apoptosis eliminates excess germ cells that acted as nurse cells to provide cytoplasmic components to maturing oocytes.

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Single cell transcriptomics reveal temporal dynamics of critical regulators of germ cell fate during mouse sex determination

10.1101/747279 ◽

2019 ◽

Cited By ~ 3

Author(s):

Chloé Mayère ◽

Yasmine Neirijnck ◽

Pauline Sararols ◽

Chris M Rands ◽

Isabelle Stévant ◽

...

Keyword(s):

Sex Determination ◽

Germ Cell ◽

Single Cell ◽

Cell Fate ◽

Gene Networks ◽

Network Inference ◽

Temporal Dynamics ◽

Intron Retention ◽

Gonad Development ◽

Altered Expression

SummaryDespite the importance of germ cell (GC) differentiation for sexual reproduction, the gene networks underlying their fate remain unclear. Here, we comprehensively characterize the gene expression dynamics during sex determination based on single-cell RNA sequencing of 14,914 XX and XY mouse GCs between embryonic days (E) 9.0 and 16.5. We found that XX and XY GCs diverge transcriptionally as early as E11.5 with upregulation of genes downstream of the Bone morphogenic protein (BMP) and Nodal/Activin pathways in XY and XX GCs, respectively. We also identified a sex-specific upregulation of genes associated with negative regulation of mRNA processing and an increase in intron retention consistent with a reduction in mRNA splicing in XY testicular GCs by E13.5. Using computational gene regulation network inference analysis, we identified sex-specific, sequential waves of putative key regulator genes during GC differentiation and revealed that the meiotic genes are regulated by positive and negative master modules acting in an antagonistic fashion. Finally, we found that rare adrenal GCs enter meiosis similarly to ovarian GCs but display altered expression of master genes controlling the female and male genetic programs, indicating that the somatic environment is important for GC function. Our data is available on a web platform and provides a molecular roadmap of GC sex determination at single-cell resolution, which will serve as a valuable resource for future studies of gonad development, function and disease.

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