It is well established that the c-kit gene plays an essential role in the proliferation of differentiating spermatogonia in prepuberal mice. However, the mechanisms that regulate the onset of spermatogenesis, i.e. differentiation of spermatogonial stem cells and c-kit expression, are poorly understood. Here we identify a novel signal transduction system in mouse prepuberal testis regulating this developmental event, involving bone morphogenetic protein 4 (BMP4) and its transduction machinery. BMP4 is produced by Sertoli cells very early in the postnatal life and is successively down regulated in peri-puberal Sertoli cells. Its receptor Alk3 and the R-Smad Smad5 are specifically expressed both in proliferating primordial germ cells and in postnatal spermatogonia. BMP4 stimulation of cultured spermatogonia induces Smad4/5 nuclear translocation and the formation of a DNA-binding complex with the transcriptional coactivator p300/CBP. In vitro exposure of undifferentiated spermatogonia to BMP4 exerts both mitogenic and differentiative effects, inducing [3H]thymidine incorporation and Kit expression. As a result of the latter event, Kit-negative spermatogonia acquire sensitivity to Stem Cell Factor.

Pellegrini, M., Grimaldi, P., Rossi, P., Geremia, R., DOLCI IANNINI, S. (2003). Developmental expression of BMP4/ALK3/SMAD5 signaling pathway in the mouse testis: a potential role of BMP4 in spermatogonia differentiation. JOURNAL OF CELL SCIENCE, 116(Pt 16), 3363-3372 [10.1242/jcs.00650].

Developmental expression of BMP4/ALK3/SMAD5 signaling pathway in the mouse testis: a potential role of BMP4 in spermatogonia differentiation

GRIMALDI, PAOLA;ROSSI, PELLEGRINO;GEREMIA, RAFFAELE;DOLCI IANNINI, SUSANNA
2003-08-15

Abstract

It is well established that the c-kit gene plays an essential role in the proliferation of differentiating spermatogonia in prepuberal mice. However, the mechanisms that regulate the onset of spermatogenesis, i.e. differentiation of spermatogonial stem cells and c-kit expression, are poorly understood. Here we identify a novel signal transduction system in mouse prepuberal testis regulating this developmental event, involving bone morphogenetic protein 4 (BMP4) and its transduction machinery. BMP4 is produced by Sertoli cells very early in the postnatal life and is successively down regulated in peri-puberal Sertoli cells. Its receptor Alk3 and the R-Smad Smad5 are specifically expressed both in proliferating primordial germ cells and in postnatal spermatogonia. BMP4 stimulation of cultured spermatogonia induces Smad4/5 nuclear translocation and the formation of a DNA-binding complex with the transcriptional coactivator p300/CBP. In vitro exposure of undifferentiated spermatogonia to BMP4 exerts both mitogenic and differentiative effects, inducing [3H]thymidine incorporation and Kit expression. As a result of the latter event, Kit-negative spermatogonia acquire sensitivity to Stem Cell Factor.
15-ago-2003
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/16 - ANATOMIA UMANA
English
Con Impact Factor ISI
Animals; p300-CBP Transcription Factors; Smad4 Protein; Cell Cycle Proteins; Testis; Carrier Proteins; Proto-Oncogene Proteins c-kit; DNA-Binding Proteins; Electrophoretic Mobility Shift Assay; Histone Acetyltransferases; Mice; Spermatogenesis; Microscopy, Fluorescence; Activin Receptors; Sertoli Cells; Transcription Factors; Phosphoproteins; Acetyltransferases; Bone Morphogenetic Proteins; Trans-Activators; Smad5 Protein; Signal Transduction; Male; Spermatogonia
Pellegrini, M., Grimaldi, P., Rossi, P., Geremia, R., DOLCI IANNINI, S. (2003). Developmental expression of BMP4/ALK3/SMAD5 signaling pathway in the mouse testis: a potential role of BMP4 in spermatogonia differentiation. JOURNAL OF CELL SCIENCE, 116(Pt 16), 3363-3372 [10.1242/jcs.00650].
Pellegrini, M; Grimaldi, P; Rossi, P; Geremia, R; DOLCI IANNINI, S
Articolo su rivista
File in questo prodotto:
File Dimensione Formato  
PellegriniJCS2003.pdf

accesso aperto

Descrizione: file pdf
Dimensione 586.75 kB
Formato Adobe PDF
586.75 kB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/51136
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 186
  • ???jsp.display-item.citation.isi??? 159
social impact