hes4
hes3
hes2
hes1
Gene
TABLE 7.10
hes Genes in the Xenopus Neural Border and Its Descendants
For the role of hes genes in placodal neurogenesis, see hes2, hes5.4 in Table 7.8 . See abbreviations in Table 7.3 legend.
Expression/Role
Gain-of-Function
Loss-of-Function
(Dominant-Negative/Morpholino)
At neural plate stage, hes1 is expressed in thin longitudinal
lines corresponding to the dorsal and ventral boundaries of
NCC ( Vega-López et al., 2015 ).
Promotes NCC at the expense of contiguous fates (neural
plate/epidermis), independently of cell proliferation during
early NCC development (Vega-López et al., 2015)
GR-hes1 (Dex s11): ↑NCC (snai2), ↓neural plate (sox2) and
non-neural ectoderm (krt12.4) (ISH neurula); proliferation
unaffected (pH3, neurula stage) (Vega-López et al., 2015).
GR-hes1 (Dex s11) +/− HUA: ↑NCC (foxd3), ↓ neural plate
(sox2) (ISH neurula) (Vega-López et al., 2015).
GR-hes1 (Dex s11): ↓NCC (snai2), ↑neural plate (sox2) and
non-neural ectoderm (krt12.4) (ISH neurula); proliferation
unaffected (pH3, neurula stage) (Vega-López et al., 2015).
GR-DN-hes1 (Dex s11) +/− HUA: ↓NCC (foxd3), ↑neural
plate (sox2) (ISH neurula) (Vega-López et al., 2015).
Scattered cells in the ectoderm/neural ectoderm (mid-gastrula)
Posterior PPE, including the prospective otic and lateral
line placodes (neural plate) ( Sölter et al., 2006 ; Riddiford
and Schlosser, 2016 ).
Strongly expressed in a domain comprising the anterior and
lateral edges of the neural plate, just adjacent to the NB
( Hong and Saint-Jeannet, 2018).
Suff cient to promote neural plate fates at the expense of NB
fates (NCC and placodes) but normal requirement still
unproven. Other genes of the Hes family might compensate
for hes3 knock-down.
GR-hes3 (Dex NF10.5):
Promoted neural plate at the expense of NB fates. Blocks
NCC induction by wnt8a DNA or β-catenin DNA
injection. In animal cap assays, blocked NCC and PPE
gene induction by Wnt8 and Noggin and promoted neural
plate fate (Hong and Saint-Jeannet, 2018).
hes3 MO: two translation-blocking MOs targeting hes3.L, one
translation-blocking MO targeting hes3.S, and one
splice-blocking MO targeting hes3.L and hes3.S, tested
alone or in different combinations, did not affect the
expression of gene markers that were affected by the gain of
function approach (Hong and Saint-Jeannet, 2018).
NB at mid-gastrula ( Tsuji et al., 2003 ).
One of the earliest PPE markers (mid-gastrula) ( Murato and
Hashimoto, 2009 ; Maharana and Schlosser, 2018 ).
Prospective NCC territories (neural plate stage) ( VegaLópez et al., 2015 )
hes4 is required during several steps of NCC development
(specif cation, maintenance, onset of migration). Only the
hes4.L homeolog is required in X. laevis.
hes4 is required for the establishment of the PPE and the
development of the lens f eld.
hes4 overexpression : ↓bmp4, ↑NCC (snai2, msx1 ) (neural
plate stage) ( Glavic et al., 2004 )
GR-hes4 (Dex NF11.5–12): ↓NCC (snai2, foxd3, sox9,
sox10), ↑neural plate (soxd), ↑NB (msx1, pax3, zic1),
↑dll1 ,
↑proliferation (pH3), ↓apoptosis (neural plate stage);
↑ and ↓ different subsets of NCC cell-types (tailbud stage)
( Nichane et al., 2008b ; Nichane et al., 2008a ).
GR-hes4.S, GR-hes4.L (Dex NF11) +/− HUA treatments,
pH3; GR-hes4.S -EnR, GR- hes4.L-EnR (Dex NF12.5) :
Hes4 acts as a transcriptional repressor, promoting NCC
specif cation at the expense of contiguous fates (neural
plate/epider
hes4 MO :
↓
markers without affecting neural plate and epidermal
NCC
markers (early neurula) ( Nagatomo and Hashimoto, 2007 )
or with ↑ of neural plate and epidermal markers ( VegaLópez et al., 2015 ). Variable changes in the expression
domains of the NCC specif er foxd3, with slight ↑sox3
(neural plate) ( Maharana and Schlosser, 2018 ).
↓
notch2
six1/eya1,
(PPE) (neural plate stage); other PPE
markers unaffected ( foxe3, dlx5) ( Maharana and Schlosser,
2018 ; Murato and Hashimoto, 2009 ); ↓lens f eld ( pax6,
six3, pitx1); malformed lens (tadpoles, NF42) ( Murato and
108
Xenopus
hes3
hes2
hes1
Gene
TABLE 7.10
hes Genes in the Xenopus Neural Border and Its Descendants
For the role of hes genes in placodal neurogenesis, see hes2, hes5.4 in Table 7.8 . See abbreviations in Table 7.3 legend.
Expression/Role
Gain-of-Function
Loss-of-Function
(Dominant-Negative/Morpholino)
At neural plate stage, hes1 is expressed in thin longitudinal
lines corresponding to the dorsal and ventral boundaries of
NCC ( Vega-López et al., 2015 ).
Promotes NCC at the expense of contiguous fates (neural
plate/epidermis), independently of cell proliferation during
early NCC development (Vega-López et al., 2015)
GR-hes1 (Dex s11): ↑NCC (snai2), ↓neural plate (sox2) and
non-neural ectoderm (krt12.4) (ISH neurula); proliferation
unaffected (pH3, neurula stage) (Vega-López et al., 2015).
GR-hes1 (Dex s11) +/− HUA: ↑NCC (foxd3), ↓ neural plate
(sox2) (ISH neurula) (Vega-López et al., 2015).
GR-hes1 (Dex s11): ↓NCC (snai2), ↑neural plate (sox2) and
non-neural ectoderm (krt12.4) (ISH neurula); proliferation
unaffected (pH3, neurula stage) (Vega-López et al., 2015).
GR-DN-hes1 (Dex s11) +/− HUA: ↓NCC (foxd3), ↑neural
plate (sox2) (ISH neurula) (Vega-López et al., 2015).
Scattered cells in the ectoderm/neural ectoderm (mid-gastrula)
Posterior PPE, including the prospective otic and lateral
line placodes (neural plate) ( Sölter et al., 2006 ; Riddiford
and Schlosser, 2016 ).
Strongly expressed in a domain comprising the anterior and
lateral edges of the neural plate, just adjacent to the NB
( Hong and Saint-Jeannet, 2018).
Suff cient to promote neural plate fates at the expense of NB
fates (NCC and placodes) but normal requirement still
unproven. Other genes of the Hes family might compensate
for hes3 knock-down.
GR-hes3 (Dex NF10.5):
Promoted neural plate at the expense of NB fates. Blocks
NCC induction by wnt8a DNA or β-catenin DNA
injection. In animal cap assays, blocked NCC and PPE
gene induction by Wnt8 and Noggin and promoted neural
plate fate (Hong and Saint-Jeannet, 2018).
hes3 MO: two translation-blocking MOs targeting hes3.L, one
translation-blocking MO targeting hes3.S, and one
splice-blocking MO targeting hes3.L and hes3.S, tested
alone or in different combinations, did not affect the
expression of gene markers that were affected by the gain of
function approach (Hong and Saint-Jeannet, 2018).
NB at mid-gastrula ( Tsuji et al., 2003 ).
One of the earliest PPE markers (mid-gastrula) ( Murato and
Hashimoto, 2009 ; Maharana and Schlosser, 2018 ).
Prospective NCC territories (neural plate stage) ( VegaLópez et al., 2015 )
hes4 is required during several steps of NCC development
(specif cation, maintenance, onset of migration). Only the
hes4.L homeolog is required in X. laevis.
hes4 is required for the establishment of the PPE and the
development of the lens f eld.
hes4 overexpression : ↓bmp4, ↑NCC (snai2, msx1 ) (neural
plate stage) ( Glavic et al., 2004 )
GR-hes4 (Dex NF11.5–12): ↓NCC (snai2, foxd3, sox9,
sox10), ↑neural plate (soxd), ↑NB (msx1, pax3, zic1),
↑dll1 ,
↑proliferation (pH3), ↓apoptosis (neural plate stage);
↑ and ↓ different subsets of NCC cell-types (tailbud stage)
( Nichane et al., 2008b ; Nichane et al., 2008a ).
GR-hes4.S, GR-hes4.L (Dex NF11) +/− HUA treatments,
pH3; GR-hes4.S -EnR, GR- hes4.L-EnR (Dex NF12.5) :
Hes4 acts as a transcriptional repressor, promoting NCC
specif cation at the expense of contiguous fates (neural
plate/epider
hes4 MO :
↓
markers without affecting neural plate and epidermal
NCC
markers (early neurula) ( Nagatomo and Hashimoto, 2007 )
or with ↑ of neural plate and epidermal markers ( VegaLópez et al., 2015 ). Variable changes in the expression
domains of the NCC specif er foxd3, with slight ↑sox3
(neural plate) ( Maharana and Schlosser, 2018 ).
↓
notch2
six1/eya1,
(PPE) (neural plate stage); other PPE
markers unaffected ( foxe3, dlx5) ( Maharana and Schlosser,
2018 ; Murato and Hashimoto, 2009 ); ↓lens f eld ( pax6,
six3, pitx1); malformed lens (tadpoles, NF42) ( Murato and
108
Xenopus