Biomedical Engineering Reference
In-Depth Information
8.6.2
FGF (Fibroblast Growth Factor) and Other Factors
In vitro
culture of the spermatogonia revealed the important role of Fibroblast
Growth Factor (FGF) signaling in the maintenance/expansion of the stem cells;
however, it is only observed in the presence of GDNF (Kanatsu-Shinohara et al.
2003
; Kubota et al.
2004
). While bFGF (FGF2) demonstrates a clear function in
these cultures, it is obscure whether FGF signaling actually plays an active role
in vivo
, and, if it does, which member of the FGF family is involved. The expres-
sion profiles of the FGF family ligands and their receptors are somewhat compli-
cated. In addition, the
in vitro
culture has revealed the effect of other factors, such
as leukemia inhibitory factor (LIF) or epidermal growth factor (EGF) (Kanatsu-
Shinohara et al.
2003, 2007
); how these factors are involved in the
in vivo
niche also
needs to be elucidated.
8.7
Cell-Cell Contact and Basement Membrane Binding
In the case of
Drosophila
germline and other stem cell systems in mammals,
cell-cell contact plays an essential role in their niches, which is mediated by
adhesion molecules such as cadherins (Song et al.
2002
). In these systems, cad-
herins tether the stem cell to the niche cells via homophilic binding. In the
mouse spermatogenesis, E-cadherin is expressed in A
undiff
(Tokuda et al.
2007
),
raising the possibility of a similar tethering mechanism via cadherin molecules
being involved in the mouse spermatogenic stem cells. However, recently,
Shinohara and colleagues clearly demonstrated that E-cadherin is dispensable
for the normal functioning of the stem cells, i.e., the transplantation of cultured
stem cells lacking E-cadherin successfully colonized the host seminiferous
tubules and supported persisting spermatogenesis (Kanatsu-Shinohara et al.
2008
). This finding agrees with the observation that E-cadherin gene expression
is not detected in Sertoli or myoid cells (Yoshida, unpublished data). Similarly,
our live imaging studies have suggested that E-cadherin-expressing A
undiff
, move
around in the testis, suggesting that they are not tethered to a fixed position
[(Yoshida et al.
2007b
) and data not shown].
In contrast, Shinohara's transplantation assay has also demonstrated the essen-
tial role of b1-integrin in posttransplantation colony formation (Kanatsu-
Shinohara et al.
2008
). b1-integrin is expressed in a spermatogonial population,
including stem cells, and mediates the attachment to the basement membrane via
binding to laminins, probably as a heterocomplex with a6-integrin (Shinohara
et al.
2000
). GS cells lacking b1-integrin fail to develop spermatogenic colonies
after transplantation. This suggests the important role of interaction with the
basement membrane in stem cell functioning. The posttransplantation homing of
stem cells and subsequent colony formation includes multiple steps (attachment
to the Sertoli cell surface, retrograde translocation to the basal compartment
across the tight junction, migration to the presumptive stem cell niche, survival,
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