title: Derivation in culture of primordial germ cells from cells of the mouse epiblast: phenotypic induction and growth control by Bmp4 signalling.
abstract: Primordial germ cells (PGCs) are the embryonic precursors of the gametes of the adult. PGCs derive from cells of the most proximal part of the cup-shaped epiblast corresponding to the presumptive region of the extraembryonic mesoderm. At 7.2 days post coitum (dpc) a small group of PGCs located at the base of the allantois can be recognised due to a strong alkaline phosphatase activity. Thus far, scant information was available on the mechanism(s) controlling the lineage of PGCs in the mouse embryo. However, results obtained in mice defective for bone morphogenetic protein-4 (Bmp4) secreted molecule revealed that this growth factor has important functions for the derivation of PGCs from extraembryonic mesoderm cells. In this paper, we have studied the effects in culture of Bmp4 on epiblast cells obtained from egg-cylinder stage mouse embryos (5.5-6.0 dpc) and PGCs from 11.5 dpc embryos. We found that Bmp4 treatment enables recruitment of pluripotent cells to a PGC phenotype by a multi-step process involving an initial pre-commitment of epiblast cells and a following stage of PGC phenotypic determination. We further provide evidences that Bmp4 may promote the growth of gonadal PGCs through a Smad1/4 signalling.
authors.affiliation: Department of Public Health and Cell Biology, Section of Histology and Embryology, University of Rome Tor Vergata, Rome, Italy. m.pesce@idi.it
authors.forename: Maurizio
authors.initials: M
authors.lastname: Pesce
authors.forename: Francesca Gioia
authors.initials: FG
authors.lastname: Klinger
authors.forename: Massimo
authors.initials: M
authors.lastname: De Felici
mesh_terms: D030201:Activin Receptors, Type I / Q000096:biosynthesis* / Q000235:genetics*; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D052005:Bone Morphogenetic Protein Receptors, Type I; D002455:Cell Division; D019070:Cell Lineage; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D005854:Germ Cells / Q000378:metabolism*; D007150:Immunohistochemistry; D051379:Mice; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases; D017978:Receptors, Growth Factor; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D051785:Smad Proteins; D051898:Smad1 Protein; D051901:Smad4 Protein; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D017978:Receptors, Growth Factor; D051785:Smad Proteins; D051898:Smad1 Protein; C497401:Smad1 protein, mouse; D051901:Smad4 Protein; C490810:Smad4 protein, mouse; D015534:Trans-Activators; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D052005:Bone Morphogenetic Protein Receptors, Type I; D000469:Alkaline Phosphatase