|
 |
|||||||||||||||||||
|
|||||||||||||||||||
|
|||||||||||||||||||
 |
 |
|
|
Drivers of Germ Cell Maturation
aMonash Institute of Medical Research, Monash University, Melbourne, Australia bDepartment of Biochemistry and Molecular Biology, Monash University, Melbourne, Australia cAustralian Research Council Centre of Excellence in Biotechnology and Development, Australia dPrince Henry's Institute of Medical Research, Melbourne Australia eDepartment of Molecular and Human Genetics and Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA
Address for correspondence: Kate Lakoski Loveland, Monash Institute of Medical Research, 27-31 Wright Street, Clayton, Victoria 3168 Australia. Voice: 61-3-9594-7418; fax: 61-3-9594-7111. Kate.loveland{at}med.monash.edu.au
Spermatogenesis requires progression of germ line stem cells through a precisely ordered differentiation pathway to form spermatozoa. Diverse and dynamic signals from the transforming growth factor-ß (TGF-ß) superfamily influence many stages of germ cell development. For example, interactions between several TGF-ß superfamily ligands (bone morphogenetic proteins, activin, and glial-derived neurotrophic growth factor [GDNF]) appear to govern the onset of spermatogenesis, and we are exploring how germ cells interpret these competing signals. We examined the in vivo impact of activin on testis development using two mouse models, the inhba–/– mouse (which lacks the gene encoding the activin A subunit and dies at birth) and BK mice, with inhbb (encoding the activin ßB subunit) replacing inhba (which survive to adulthood and show delayed fertility onset in males). Distinct effects on Sertoli cell and germ cell populations during fetal and early postnatal development were measured. We recognize that specific proteins, including downstream targets of TGF-ß signals, such as Smads, must move into the nucleus to implement the gene transcription changes required for development. We hypothesized that changes at the level of cellular nuclear transport machinery may be required to mediate this. Examination of proteins involved in classical nuclear import, the importins, revealed that each importin has a developmentally regulated expression pattern in male germ cells. Because each importin binds a selected range of cargo proteins and mediates their nucleocytoplasmic passage, our findings suggest that each importin ferries cargo required for discrete stages of spermatogenesis.
Key Words: activin • importins • spermatogenesis • nuclear transport • Sertoli cells • Smads • stereology • nuclear import • TGF-ß superfamily This article has been cited by other articles:
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
 |
 |
