Biomedical Engineering Reference
In-Depth Information
Table 7.1
Transcription factors implicated as important regulators in SSC function
GDNF
regulated
a
Fertility
phenotype
b
Gene
Germline defect
Citations
Bcl6b
Y
Sub-fertile
Loss of spermatogonia,
Sertoli cell only
phenotype
Oatley et al.
(
2006
)
C-Fos
Y
Sub-fertile
Impaired development
of meiotic germ
cells
Johnson et al.
(1992)
Etv5
Y
Infertile
Loss of spermatogonia
Sertoli cell only
phenotype
Chen et al. (
2005
)
Lhx1
Y
N/A
c
Lack gonads
Shawlot and
Behringer
1995
Ngn3
N
Undetermined
Undetermined
Gradwohl et al.
(2000)
n-Myc
N
N/A
c
Undetermined
Charron et al.
(
1992
)
Plzf
N
Infertile
Loss of spermatogonia,
Sertoli cell only
phenotype
Buaas et al.
(
2004
)
Costoya et al.
(
2004
)
Sohlh1
N
Infertile
Disrupted spermatogonial
differentiation
Ballow et al.
(
2006
)
Taf4b
N
Infertile
Loss of spermatogonia,
Sertoli cell only
phenotype
Falender et al.
(
2005
)
a
Based on microarray analysis of GDNF-regulated genes in cultured mouse SSCs
(Oatley et al.
2006
)
b
As documented in knock-out mouse models
c
Embryonic/neonatal lethality
been the importance of specific transcription factor encoding genes that regulate
mouse SSC fate decisions (Table
7.1
).
7.3.1
GDNF-Regulated Gene Expression in Mouse SSCs
Because GDNF is regarded as an essential extrinsic stimulator of SSC self-renewal,
recent examination of internal molecular mechanisms regulating SSC fate decisions
have focused on those activated or suppressed by GDNF stimulation. Using a DNA
microarray approach, GDNF-regulated gene expression was explored in cultured
mouse SSCs (Oatley et al.
2006
). Expression levels of specific genes that dramati-
cally decreased upon GDNF withdrawal and increased following GDNF replace-
ment were identified. In total, expressions of 79 genes were up-regulated twofold
or greater by GDNF stimulation (Oatley et al.
2006
). Those showing the greatest
level of GDNF-regulation included three transcription factors, B cell CLL/
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