Talk:Primordial Germ Cell Migration Movie
BMP signaling controls formation of a primordial germ cell niche within the early genital ridges
Dev Biol. 2010 Jul 1;343(1-2):84-93. doi: 10.1016/j.ydbio.2010.04.011. Epub 2010 Apr 22.
Dudley B, Palumbo C, Nalepka J, Molyneaux K. Source Department of Genetics, Case Western Reserve University, Cleveland, OH, USA.
Stem cells are necessary to maintain tissue homeostasis and the microenvironment (a.k.a. the niche) surrounding these cells controls their ability to self-renew or differentiate. For many stem cell populations it remains unclear precisely what cells and signals comprise a niche. Here we identify a possible PGC niche in the mouse genital ridges. Conditional ablation of Bmpr1a was used to demonstrate that BMP signaling is required for PGC survival and migration as these cells colonize the genital ridges. Reduced BMP signaling within the genital ridges led to increased somatic cell death within the mesonephric mesenchyme. Loss of these supporting cells correlated with decreased levels of the mesonephric marker, Pax2, as well as a reduction in genes expressed in the coelomic epithelium including the putative PGC chemo-attractants Kitl and Sdf1a. We propose that BMP signaling promotes mesonephric cell survival within the genital ridges and that these cells support correct development of the coelomic epithelium, the target of PGC migration. Loss of BMP signaling leads to the loss of the PGC target resulting in reduced PGC numbers and disrupted PGC migration. Copyright 2010 Elsevier Inc. All rights reserved.
The roles of FGF signaling in germ cell migration in the mouse
Development. 2005 Dec;132(24):5399-409. Epub 2005 Nov 16.
Takeuchi Y, Molyneaux K, Runyan C, Schaible K, Wylie C. Source Department of Marine Biosciences, Tokyo University of Marine Science and Technology, 4-5-7 Konan, Minato-ku, Tokyo 108-8477, Japan.
Fibroblast growth factor (FGF) signaling is thought to play a role in germ cell behavior. FGF2 has been reported to be a mitogen for primordial germ cells in vitro, whilst combinations of FGF2, steel factor and LIF cause cultured germ cells to transform into permanent lines of pluripotent cells resembling ES cells. However, the actual function of FGF signaling on the migrating germ cells in vivo is unknown. We show, by RT-PCR analysis of cDNA from purified E10.5 germ cells, that germ cells express two FGF receptors: Fgfr1-IIIc and Fgfr2-IIIb. Second, we show that FGF-mediated activation of the MAP kinase pathway occurs in germ cells during their migration, and thus they are potentially direct targets of FGF signaling. Third, we use cultured embryo slices in simple gain-of-function experiments, using FGF ligands, to show that FGF2, a ligand for FGFR1-IIIc, affects motility, whereas FGF7, a ligand for FGFR2-IIIb, affects germ cell numbers. Loss of function, using a specific inhibitor of FGF signaling, causes increased apoptosis and inhibition of cell shape change in the migrating germ cells. Lastly, we confirm in vivo the effects seen in slice cultures in vitro, by examining germ cell positions and numbers in embryos carrying a loss-of-function allele of FGFR2-IIIb. In FGFR2-IIIb(-/-) embryos, germ cell migration is unaffected, but the numbers of germ cells are significantly reduced. These data show that a major role of FGF signaling through FGFR2-IIIb is to control germ cell numbers. The data do not discriminate between direct and indirect effects of FGF signaling on germ cells, and both may be involved. PMID 16291796
Primordial germ cell migration
Int J Dev Biol. 2004;48(5-6):537-44.
Molyneaux K, Wylie C. Source Division of Developmental Biology, Children's Hospital Research Foundation, Cincinnati, Ohio 45229, USA.
Mutational and antisense screens in Drosophila and zebrafish, and transcriptional profiling and time-lapse analysis in the mouse, have contributed greatly to our understanding of PGC development. In all three systems, the behavior of PGCs is controlled by growth factors which signal through G-protein coupled receptors and/or tyrosine kinase receptors. Additionally, regulated cell-cell and cell-substrate adhesion is important for PGC motility. Finally, localized growth factors may control PGC survival and consequently PGC position. Chemotaxis, regulated adhesion and cell survival are important for multiple migration processes which occur during development and disease. PGC migration shares these features. PMID 15349828