BMP signaling regulates PGC numbers and motility in organ culture.
Members of the bone morphogenetic protein (BMP) family play diverse roles in multiple developmental processes. However, in the mouse, mutations in many BMPs, BMP receptors and signaling components result in early embryonic lethality making it difficult to analyze the role of these factors during organogenesis or tissue homeostasis in the adult. To bypass this early lethality, we used an organ culture system to study the role of BMPs during primordial germ cell (PGC) migration. PGCs are the embryonic precursors of the sperm and eggs. BMPs induce formation of primordial germ cells within the proximal epiblast of embryonic day 7.5 (E7.5) mouse embryos. PGCs then migrate via the gut to arrive at the developing gonads by E10.5. Addition of BMP4 or the BMP-antagonist Noggin to transverse slices dissected from E9.5 embryos elevated PGC numbers or reduced PGC numbers, respectively. Noggin treatment also slowed and randomized PGC movements, resulting in a failure of PGCs to colonize the urogenital ridges (UGRs). Based on p-Smad1/5/8 staining, migratory PGCs do not respond to endogenous BMPs. Instead, the somatic cells of the urogenital ridges exhibit elevated p-Smad1/5/8 staining revealing active BMP signaling within the UGRs. Noggin treatment abrogated p-Smad staining within the UGRs and blocked localized expression of Kitl, a cytokine known to regulate the survival and motility of PGCs and Id1, a transcription factor expressed within the UGRs. We propose that BMP signaling regulates PGC migration by controlling gene expression within the somatic cells along the migration route and within the genital ridges.
Dudley
Brian M
BM
Department of Genetics, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH 44106, USA.
Runyan
Chris
C
Takeuchi
Yutaka
Y
Schaible
Kyle
K
Molyneaux
Kathleen
K
D000818:Animals; D055415:Bone Morphogenetic Protein 4; D055417:Bone Morphogenetic Protein 5; D052004:Bone Morphogenetic Protein Receptors / Q000235:genetics / Q000378:metabolism; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D002352:Carrier Proteins / Q000494:pharmacology; D002452:Cell Count; D002465:Cell Movement / Q000502:physiology; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D005854:Germ Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051798:Inhibitor of Differentiation Protein 1 / Q000235:genetics; D008297:Male; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism; D008650:Mesonephros / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009924:Organ Culture Techniques; D011247:Pregnancy; D015398:Signal Transduction; D051785:Smad Proteins / Q000235:genetics / Q000378:metabolism; D019089:Stem Cell Factor / Q000235:genetics; D000099176:Noggin Protein
D055415:Bone Morphogenetic Protein 4; D055417:Bone Morphogenetic Protein 5; D052004:Bone Morphogenetic Protein Receptors; D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D051798:Inhibitor of Differentiation Protein 1; D051785:Smad Proteins; D019089:Stem Cell Factor; D000099176:Noggin Protein; C525810:Bmp4 protein, mouse; C525815:Bmp5 protein, mouse; C497455:Idb1 protein, mouse