103
TABLE 7.8
Role of hes/hey Genes in Xenopus Neurogenesis and Epidermal Differentiation
See abbreviations in Table 7.3 legend and marker details in Table 7.7 legend.
Role/Details
Gain-of-Function
Loss-of-Function
(Dominant-Negative/Morpholino)
hes5.4
hes5.1
hes4
hes2
hes1
Gene
Inhibits neurogenesis by abolishing the activity of proneural/
neuronal differentiation bHLH TFs and keeping neural
progenitors in a proliferative state, independently of
binding to TLE/Groucho co-repressors.
Hes1 binds to N-box in vitro (Koyano-Nakagawa et al., 2000)
and does not block the ability of Neurog2 to bind DNA or
its coactivator E12 in vitro (Murai et al., 2011).
hes1 overexpression: ↑sox2 [not shown in (Nichane et al.,
2008a)], induced ectopic dll1 [not shown in (Nichane et al.,
2008b )], ↓PN by abolishing Neurog2 and Neurod1 activity
(Murai et al., 2011).
mir-9 MO and hes1 target protector MO: ↓neurogenesis
(NF30), ↑proliferation (Bonev et al., 2011).
hes1-ΔWRPW: did not suppress PN (Murai et al., 2011).
Inhibits PN by repressing proneural gene transcription and
other mechanisms such as binding to proneural bHLH
proteins like NeuroD.
In the retina, hes2 promotes gliogenesis and inhibits
neurogenesis through a DNA-binding mechanism.
Immunoprecipitation in animal cap explants: XHes2 interacts
with XNeuroD1, XNeuroD4, XHes1, and XHes6 but not with
other bHLH proteins tested, including XNeurog2 (Sölter et al.,
2006 ).
hes2:
mRNA overexpression: ↓PN, ↓ neurog2 ( Sölter
et al., 2006 ).
Local overexpression by in vivo DNA lipofection in the
developing retina: ↑glial population at the expense of
neurons (Sölter et al., 2006).
Hes2-ΔW-VP16:
mRNA: induced ectopic primary sensory neurons and
neurog2 (Sölter et al., 2006).
In vivo lipofection of Hes2-ΔW-VP16 DNA: ↓glial population,
↑
neuronal types ( Sölter et al., 2006 ).
some
hes2 DBM: did not affect retinal fates; DNA binding domain
necessary for promoting gliogenesis in the retina ( Sölter et al.,
2006 ).
hes2 MO:
↑neurog2 in presumptive otic placode. In vivo lipofection of
hes2 MOs ↓glial population in the retina (Sölter et al., 2006).
Inhibits PN.
Hes4 protein binds to N-box in vitro (electrophoretic mobility
shift assay) ( Koyano-Nakagawa
et al., 2000 ).
hes4 overexpression : ↓PN (tubb2b, neural plate stage) ( Glavic
et al., 2004 ) ( Cui, 2005 ); ↓neurog2 and neurod1 in the
anterior neural plate ( Andreazzoli et al., 2003 ; Cui, 2005 );
↑dll1 independently of DNA binding (neural plate stage)
( Nichane et al., 2008b ); blocked the induction of tubb2b by
neurog2/noggin in animal caps (NF unknown, RT-PCR)
( Cui, 2005 ).
hGR-hes4 (Dex NF18): ↓PN (ISH tubb2b, neurula stage)
( Taelman et al., 2006 ).
hes4 MO: ↑ neurog2, myt1, and dll1; ↑PN in the trigeminal
placode (early neurula) ( Nagatomo and Hashimoto, 2007 ;
Murato and Hashimoto, 2009 ); ↓proliferation, ↑apoptosis
(late neurula) ( Nagatomo and Hashimoto, 2007 ); ↓dll1
(neural plate stage) ( Nichane et al., 2008b ).
Inhibits PN probably by repressing bHLH proneural genes
through DNA binding and recruitment of the co-repressor
TLE/Groucho.
The DNA binding domain and the WRPW motif are necessary
for inhibiting PN and preventing ectopic neurogenesis
induced by the bHLH TF Atoh7 ( Schneider et al., 2001 ).
hes5.1 overexpression: ↓PN, even in the presence of the
bHLH TF Atoh7 (ISH, neural plate stage) ( Schneider et al.,
2001 ).
hes5.1 ΔWRPW: ↑PN [data not shown in ( Ito et al., 2007a )].
hes5.1 ΔWRPW or hes5.1 ΔN (basic domain deleted) : did not
prevent ectopic PN induced by the bHLH TF Atoh7 (ISH,
neural plate stage) ( Schneider et al., 2001 ).
During placodal development, hes5.4 restricts the neurogenesis hes5.4 overexpression: ↓neurog1, neurog2, neurod1, and
hes5.4 MO: ↑hes5.4, neurog1, neurog2, dll1, and pou4f1.2
cascade upstream of proneural genes. Required for the
tubb2b in the neural plate and placodes; ↓ neural marker
placodal domains with occasional reductions of these
expression of the neural progenitor gene sox3 and neuronal
sox3 in placodes (ISH, neural plate) ( Riddiford and
markers; ↓placodal sox3, neurod1, and tubb2b ( Riddiford
differentiation downstream of proneural genes.
Schlosser, 2017 ).
and Schlosser, 2017 ).
(Continued)
Notch Signaling in Early Embryogenesis
TABLE 7.8
Role of hes/hey Genes in Xenopus Neurogenesis and Epidermal Differentiation
See abbreviations in Table 7.3 legend and marker details in Table 7.7 legend.
Role/Details
Gain-of-Function
Loss-of-Function
(Dominant-Negative/Morpholino)
hes5.4
hes5.1
hes4
hes2
hes1
Gene
Inhibits neurogenesis by abolishing the activity of proneural/
neuronal differentiation bHLH TFs and keeping neural
progenitors in a proliferative state, independently of
binding to TLE/Groucho co-repressors.
Hes1 binds to N-box in vitro (Koyano-Nakagawa et al., 2000)
and does not block the ability of Neurog2 to bind DNA or
its coactivator E12 in vitro (Murai et al., 2011).
hes1 overexpression: ↑sox2 [not shown in (Nichane et al.,
2008a)], induced ectopic dll1 [not shown in (Nichane et al.,
2008b )], ↓PN by abolishing Neurog2 and Neurod1 activity
(Murai et al., 2011).
mir-9 MO and hes1 target protector MO: ↓neurogenesis
(NF30), ↑proliferation (Bonev et al., 2011).
hes1-ΔWRPW: did not suppress PN (Murai et al., 2011).
Inhibits PN by repressing proneural gene transcription and
other mechanisms such as binding to proneural bHLH
proteins like NeuroD.
In the retina, hes2 promotes gliogenesis and inhibits
neurogenesis through a DNA-binding mechanism.
Immunoprecipitation in animal cap explants: XHes2 interacts
with XNeuroD1, XNeuroD4, XHes1, and XHes6 but not with
other bHLH proteins tested, including XNeurog2 (Sölter et al.,
2006 ).
hes2:
mRNA overexpression: ↓PN, ↓ neurog2 ( Sölter
et al., 2006 ).
Local overexpression by in vivo DNA lipofection in the
developing retina: ↑glial population at the expense of
neurons (Sölter et al., 2006).
Hes2-ΔW-VP16:
mRNA: induced ectopic primary sensory neurons and
neurog2 (Sölter et al., 2006).
In vivo lipofection of Hes2-ΔW-VP16 DNA: ↓glial population,
↑
neuronal types ( Sölter et al., 2006 ).
some
hes2 DBM: did not affect retinal fates; DNA binding domain
necessary for promoting gliogenesis in the retina ( Sölter et al.,
2006 ).
hes2 MO:
↑neurog2 in presumptive otic placode. In vivo lipofection of
hes2 MOs ↓glial population in the retina (Sölter et al., 2006).
Inhibits PN.
Hes4 protein binds to N-box in vitro (electrophoretic mobility
shift assay) ( Koyano-Nakagawa
et al., 2000 ).
hes4 overexpression : ↓PN (tubb2b, neural plate stage) ( Glavic
et al., 2004 ) ( Cui, 2005 ); ↓neurog2 and neurod1 in the
anterior neural plate ( Andreazzoli et al., 2003 ; Cui, 2005 );
↑dll1 independently of DNA binding (neural plate stage)
( Nichane et al., 2008b ); blocked the induction of tubb2b by
neurog2/noggin in animal caps (NF unknown, RT-PCR)
( Cui, 2005 ).
hGR-hes4 (Dex NF18): ↓PN (ISH tubb2b, neurula stage)
( Taelman et al., 2006 ).
hes4 MO: ↑ neurog2, myt1, and dll1; ↑PN in the trigeminal
placode (early neurula) ( Nagatomo and Hashimoto, 2007 ;
Murato and Hashimoto, 2009 ); ↓proliferation, ↑apoptosis
(late neurula) ( Nagatomo and Hashimoto, 2007 ); ↓dll1
(neural plate stage) ( Nichane et al., 2008b ).
Inhibits PN probably by repressing bHLH proneural genes
through DNA binding and recruitment of the co-repressor
TLE/Groucho.
The DNA binding domain and the WRPW motif are necessary
for inhibiting PN and preventing ectopic neurogenesis
induced by the bHLH TF Atoh7 ( Schneider et al., 2001 ).
hes5.1 overexpression: ↓PN, even in the presence of the
bHLH TF Atoh7 (ISH, neural plate stage) ( Schneider et al.,
2001 ).
hes5.1 ΔWRPW: ↑PN [data not shown in ( Ito et al., 2007a )].
hes5.1 ΔWRPW or hes5.1 ΔN (basic domain deleted) : did not
prevent ectopic PN induced by the bHLH TF Atoh7 (ISH,
neural plate stage) ( Schneider et al., 2001 ).
During placodal development, hes5.4 restricts the neurogenesis hes5.4 overexpression: ↓neurog1, neurog2, neurod1, and
hes5.4 MO: ↑hes5.4, neurog1, neurog2, dll1, and pou4f1.2
cascade upstream of proneural genes. Required for the
tubb2b in the neural plate and placodes; ↓ neural marker
placodal domains with occasional reductions of these
expression of the neural progenitor gene sox3 and neuronal
sox3 in placodes (ISH, neural plate) ( Riddiford and
markers; ↓placodal sox3, neurod1, and tubb2b ( Riddiford
differentiation downstream of proneural genes.
Schlosser, 2017 ).
and Schlosser, 2017 ).
(Continued)
Notch Signaling in Early Embryogenesis