BMP Signaling in the Human Fetal Ovary is Developmentally Regulated and Promotes Primordial Germ Cell Apoptosis
| Autor: | Richard A. Anderson, Rosemary A.L. Bayne, Craig S. Collins, Hazel L. Kinnell, Andrew J. Childs, Kirsten Hogg, Alan S. McNeilly, Samira J. Green |
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| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Oocyte
Bone Morphogenetic Protein 7 Bone Morphogenetic Protein 2 Fluorescent Antibody Technique Apoptosis Bone Morphogenetic Protein 4 Biology Bone morphogenetic protein Tissue Culture Techniques Fetus Pregnancy Primordial germ cell medicine Humans Tissue-Specific Stem Cells Induced pluripotent stem cell Cell Proliferation Homeodomain Proteins MSX1 Transcription Factor Reverse Transcriptase Polymerase Chain Reaction Ovary Hematology Cell Biology Embryonic stem cell Molecular biology Immunohistochemistry Cell biology medicine.anatomical_structure Germ Cells Bone morphogenetic protein 4 embryonic structures Bone Morphogenetic Proteins Molecular Medicine Female Germ line development Stem cell Germ cell SMAD Developmental Biology |
| Zdroj: | Stem Cells (Dayton, Ohio) Childs, A J, Kinnell, H L, Collins, C S, Hogg, K, Bayne, R A L, Green, S J, McNeilly, A S & Anderson, R A 2010, ' BMP Signaling in the Human Fetal Ovary is Developmentally Regulated and Promotes Primordial Germ Cell Apoptosis ', STEM CELLS, vol. 28, no. 8, pp. 1368-1378 . https://doi.org/10.1002/stem.440 |
| ISSN: | 1549-4918 1066-5099 |
| DOI: | 10.1002/stem.440 |
| Popis: | Primordial germ cells (PGCs) are the embryonic precursors of gametes in the adult organism, and their development, differentiation, and survival are regulated by a combination of growth factors collectively known as the germ cell niche. Although many candidate niche components have been identified through studies on mouse PGCs, the growth factor composition of the human PGC niche has not been studied extensively. Here we report a detailed analysis of the expression of components of the bone morphogenetic protein (BMP) signaling apparatus in the human fetal ovary, from postmigratory PGC proliferation to the onset of primordial follicle formation. We find developmentally regulated and reciprocal patterns of expression of BMP2 and BMP4 and identify germ cells to be the exclusive targets of ovarian BMP signaling. By establishing long-term cultures of human fetal ovaries in which PGCs are retained within their physiological niche, we find that BMP4 negatively regulates postmigratory PGC numbers in the human fetal ovary by promoting PGC apoptosis. Finally, we report expression of both muscle segment homeobox (MSX)1 and MSX2 in the human fetal ovary and reveal a selective upregulation of MSX2 expression in human fetal ovary in response to BMP4, suggesting this gene may act as a downstream effector of BMP-induced apoptosis in the ovary, as in other systems. These data reveal for the first time growth factor regulation of human PGC development in a physiologically relevant context and have significant implications for the development of cultures systems for the in vitro maturation of germ cells, and their derivation from pluripotent stem cells. |
| Databáze: | OpenAIRE |
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