Formation of tubular structures relies upon complex interactions between adjacent epithelium and mesenchyme. In the embryonic testes, dramatic compartmentalization leads to the formation of testis cords (epithelium) and the surrounding interstitium (mesenchyme). Sertoli cells, the epithelial cell type within testis cords, produce signaling molecules to orchestrate testis cord formation. The interstitial fetal Leydig cells, however, are thought only to masculinize the embryo and are not known to be involved in testis cord morphogenesis. Contrary to this notion, we have identified activin A, a member of the TGF-beta protein superfamily, as a product of the murine fetal Leydig cells that acts directly upon Sertoli cells to promote their proliferation during late embryogenesis. Genetic disruption of activin betaA, the gene encoding activin A, specifically in fetal Leydig cells resulted in a failure of fetal testis cord elongation and expansion due to decreased Sertoli cell proliferation. Conditional inactivation of Smad4, the central component of TGF-beta signaling, in Sertoli cells led to testis cord dysgenesis and proliferative defects similar to those of Leydig cell-specific activin betaA knockout testes. These results indicate that activin A is the major TGF-beta protein that acts directly on Sertoli cells. Testicular dysgenesis in activin betaA and Smad4 conditional knockout embryos persists into adulthood, leading to low sperm production and abnormal testicular histology. Our findings challenge the paradigm that fetal testis development is solely under the control of Sertoli cells, by uncovering an active and essential role of fetal Leydig cells during testis cord morphogenesis.
We explore an approach for studying epistasis
In humans using a Drosophila melanogaster model of neonatal diabetes mellitus.
Expression of mutant preproinsulin, hINSC96Y, in the eye imaginal disc mimics
The human disease activating conserved cell stress response pathways leading to
Cell death and re...
We find a substantially enhanced neutron production rate. The
Scattering wave function should replace the bound state wave function for
Estimates of the enhanced neutron production rate on water plasma drenched
Cathodes of chemical cells....
We identified novel SF-1 target genes using a genome-wide promoter tiling array and a DNA microarray. SF-1 was found to regulate human glutathione S-transferase A (GSTA) family genes (hGSTA1-hGSTA4), a superfamily of detoxification enzymes clustered on chromosome 6p12. All hGSTA genes were up-regula...
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