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Published on: February 11, 2015
Altered primordial germ cell migration in the absence of transforming growth factor beta signaling via ALK5
Susana M Chuva de Sousa Lopes1, Sander van den Driesche, Rita L C Carvalho
1Hubrecht Laboratory, Netherlands Institute of Developmental Biology, Utrecht, The Netherlands.
Abstract:
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.
Insights
Transforming growth factor beta (TGFbeta) does not attract or affect primordial germ cell (PGC) migration in vivo. Its absence unexpectedly facilitates PGC migration by reducing collagen I deposition around the hindgut.
Area of Science:
- Developmental Biology
- Cell Biology
- Reproductive Biology
Background:
- Transforming growth factor beta (TGFbeta) is known to inhibit primordial germ cell (PGC) proliferation and promote their migration in vitro.
- The in vivo effects of TGFbeta on PGC behavior remain largely unclear.
Purpose of the Study:
- To investigate the in vivo role of TGFbeta signaling in regulating primordial germ cell (PGC) migration and proliferation.
- To elucidate the mechanisms underlying TGFbeta's influence on PGCs during embryonic development.
Main Methods:
- Analysis of PGC behavior in Alk5-deficient mutant embryos lacking functional TGFbeta signaling.
- Assessment of PGC migration towards gonadal ridges up to embryonic day 10.
- Evaluation of collagen type I deposition surrounding the embryonic hindgut in mutant and wild-type embryos.
Main Results:
- In vivo, TGFbeta did not act as a chemoattractant for PGCs and did not affect their proliferation during migration.
- Absence of TGFbeta signaling in Alk5-deficient embryos significantly facilitated PGC migration out of the hindgut.
- Reduced deposition of collagen type I around the hindgut of mutant embryos was observed, potentially decreasing PGC adhesion and aiding migration.
Conclusions:
- TGFbeta signaling plays a distinct role in PGC migration in vivo compared to in vitro observations.
- Reduced collagen type I deposition in the absence of TGFbeta signaling facilitates PGC migration by altering their adhesion to the hindgut environment.
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