Molecular Mechanisms Regulating Spermatogonial Stem Cell Fate Decisions - Male Germline Stem Cells Developmental and Regenerative Potential - page 149

7.3.3.5 TAF4B

Transcription activity of RNA polymerase II requires the general transcription
factor complex TFIID, which is composed of TBP and TAFII subunits. TBP associ-
ated factor 4b (TAF4B) is a component of this complex and expressed in select
tissues including the testis (Verrijzer and Tjian 1996 ). Disruption of Taf4b expres-
sion impairs fertility in both male (Falender et al. 2005 ) and female mice (Freiman
et al. 2001 ). In males, inactivation of Taf4b expression causes formation of semi-
niferous tubules with a Sertoli-cell-only phenotype (Falender et al. 2005 ). Similar
to Plzf −/− mice, Taf4b −/− mice are fertile initially with normal spermatogenesis but
seminiferous tubules deficient of germ cells gradually appear in accordance with
advancing age indicating a role in maintenance of normal SSC functions (Falender
et al. 2005 ). Under natural mating conditions, Taf4b −/− mice sire a similar number
of litters compared to TAF4B expressing mice when exposed to wild-type females
at 1 month of age; however, at 2-6 months of age Taf4b −/− mice fail to sire offspring
(Falender et al. 2005 ). Functional transplantation experiments showed that wild-
type germ cells are capable of undergoing normal spermatogenesis in testes of
Taf4b −/− males, indicating that fertility defects due to TAF4B deficiency are inherent
to the germ cells (Falender et al. 2005 ).
In the mouse germline, TAF4B expression is localized to multiple spermatogonial
sub-types including proliferating spermatogonia (A s , A pr , A al ) and differentiating
spermatogonia, in addition to round and elongating spermatids (Falender et al.
2005 ). Because of this diverse expression in a multitude of germ cells it is unlikely
that TAF4B has an SSC-specific function. Formation of a Sertoli-cell-only pheno-
type could be a secondary response by Sertoli cells to rid the seminiferous epithe-
lium of degenerating germ cells and not due specifically to failed SSC self-renewal.
Similar to Plzf , Taf4b expression is not regulated by GDNF in cultured mouse SSCs
(Oatley et al. 2006 ) and whether its expression is important for SSC self-renewal
in vitro has not been defined. Alternatively, TAF4B could play distinct roles in germ
cells at different stages of development.

7.3.4 Transcription Factors with Putative Roles

in SSC Differentiation

While several genes have been examined for their role in SSC self-renewal, little
advancement in the knowledge of those involved in SSC differentiation has been
made. Because GDNF has an essential role in promoting SSC self-renewal one
could reason that genes suppressed by GDNF stimulation would be those that
encode for molecules essential for SSC differentiation. In cultured SSC-containing
germ cell populations, exposure to GDNF suppressed the expression of 79 tran-
scripts (Oatley et al. 2006 ). Currently, the roles of these genes have not been studied
in detail. However, a few genes including Neurogenin 3 ( Ngn3 ) and spermatogenesis