Altered primordial germ cell migration in the absence of transforming growth factor beta signaling via ALK5.
Transforming growth factor beta (TGFbeta) inhibits proliferation and promotes the migration of primordial germ cells (PGCs) towards explants of gonadal ridges in vitro. However, its effects in vivo are still unclear. Here, we analyzed the behavior of PGCs in embryos lacking TGFbeta signaling via the type I receptor ALK5. TGFbeta in vivo was neither a chemoattractant for PGCs, nor did it affect their proliferation during migration towards the gonadal ridges up to embryonic day (E)10. Unexpectedly, the absence of TGFbeta signaling in fact resulted in significant facilitation of PGC migration out of the hindgut, due to the reduced deposition of collagen type I surrounding the gut of Alk5-deficient mutant embryos. Migratory PGCs adhere strongly to collagen; therefore, reduced collagen type I along the gut may result in reduced adhesion, facilitating migration into the dorsal mesenterium and gonadal ridges. Our results provide new evidence for the role of TGFbeta signaling in migration of PGCs in vivo distinct from that described previously.
Chuva de Sousa Lopes
Susana M
SM
Hubrecht Laboratory, Netherlands Institute of Developmental Biology, Utrecht, The Netherlands.
van den Driesche
Sander
S
Carvalho
Rita L C
RL
Larsson
Jonas
J
Eggen
Bart
B
Surani
M Azim
MA
Mummery
Christine L
CL
D030201:Activin Receptors, Type I / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D024042:Collagen Type I / Q000502:physiology; D017931:DNA Primers; D047108:Embryonic Development / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D005854:Germ Cells / Q000502:physiology*; D007150:Immunohistochemistry; D051379:Mice; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D024042:Collagen Type I; D017931:DNA Primers; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625842:Tgfbr1 protein, mouse