83
Notch Signaling in Early Embryogenesis
TABLE 7.3
Experimental Evidence for the Responsiveness of hes1–7 and hey Genes to the Notch Pathway in Xenopus
No references were found for hes5.8, hes5.9, and hey2 regulation by the Notch pathway in Xenopus, and therefore they are not listed in this table. Abbreviations for Tables 7.3 to 7.12 : AP, anterior-posterior; aPM,
anterior prechordal mesoderm; ANB, anterior neural border; bHLH, basic helix-loop-helix; ChIP, chromatin immunoprecipitation; CHX, cycloheximide (an inhibitor of protein synthesis); Dex, dexamethasone;
DIMZ, dorsal involuting marginal zone; dll1 STU, antimorph of dll1, lacking the intracellular domain ( Chitnis et al., 1995 ); DML, dorsal midline; DMZ, dorsal marginal zone; DN, dominant-negative; DBM, DNA
binding mutant; DNIMZ, dorsal non-involuting marginal zone; E1A constructs, protein of interest fused to the activation domain of the human type 5 adenovirus E1a protein; EnR constructs, protein of interest fused
to the Drosophila Engrailed repressor domain; ER-constructs, hormone-inducible forms of proteins with nuclear functions under the control of the ligand-binding domain of the human estrogen receptor. These
recombinant fusion proteins translocate to the cell nucleus when estradiol (E2) is added to the culture medium at the desired NF stage; FP, f oor plate (ventral midline of the neural tube); GO, gastrula organizer;
GR-constructs, hormone-inducible forms of proteins with nuclear functions under the control of the ligand-binding domain of the human glucocorticoid receptor. These recombinant fusion proteins translocate to the
cell nucleus when Dex is added to the culture medium at the desired NF stage; GR- NICD1–22: hormone-inducible form of the X. laevis Notch1 intracellular domain ( Wettstein et al., 1997 ); HDAC, histone
deacetylase; HUA, hydroxyurea and aphidicolin (strong inhibitors of cell proliferation); ICD, intracellular domain; IMZ, involuting marginal zone; ISH, in situ hybridization; MHB, midbrain/hindbrain boundary;
MO, antisense morpholino oligonucleotide; NB, neural border; NCCs, neural crest cells; NF, Nieuwkoop and Faber stage of development in Xenopus; NICD, Notch intracellular domain (NICD constructs are
constitutively active); NIMZ, non-involuting marginal zone; notch1-ΔE, notch1 construct without most of the extracellular domain, constitutively active; pH3, phosphorylated form of histone H3 (marker of cell
proliferation); PN, primary neurogenesis; PPE, pre-placodal ectoderm; pPM, posterior prechordal mesoderm; PSM, presomitic mesoderm; RA, retinoic acid; RAR, retinoic acid receptor; RBPJ, recombination signal
binding protein for immunoglobulin kappa J region, transcription factor that mediates canonical Notch signaling; RBPJ-Ank: constitutively active form of the transcription factor RBPJ, consisting of the X. laevis
Notch1 ankyrin repeats fused to the C-terminus of X. laevis RBPJ ( Wettstein et al., 1997 ); RBPJ DBM, DNA binding mutant form of X. laevis RBPJ that binds to NICD but lacks the ability to bind target sites in the
DNA and acts as a dominant-negative protein by forming non-functional complexes ( Wettstein et al., 1997 ); sq, semiquantitative; TBD, tailbud region of the presomitic mesoderm; TF, transcription factor; TZ,
transition zone of the presomitic mesoderm; VMZ, ventral marginal zone; Δ, deletion; ↑up-regulation, expansion, or increase; ↓down-regulation, reduction, or decrease.
Regulated by
Regulation/Details
Gain-of-Function
Loss-of-Function
(Dominant-Negative/Antagonist/Morpholino)
dll1/
Positive in pronephros and neural plate.
GR-RBPJ-Ank, Dex NF18: ↑hes1 in pronephros ( Taelman RBPJ DBM :
↓ hes1 in pronephros ( Taelman et al., 2006 ).
notch/
et al., 2006 ).
dll1 STU :
↓hes1 in neural plate domains ( Yan
RBPJ
GR-RBPJ-Ank, Dex unstated stage : ↑hes1 neural plate
et al., 2009 ; Vega-López et al., 2015 ).
domains ( Vega-López et al., 2015 ).
notch1/
Positive in NB.
NICD1 or RBPJ-Ank : ectopic hes2 restricted to the lateral
RBPJ
border of the neural plate ( Sölter et al., 2006 ).
notch1
Positive.
NICD1: ↑hes3 (NF18, microarray) ( Vasiliu et al.,
2015 ).
dll1/
Positive in NB/NCC.
NICD1 : ↑NB hes4 domain (gastrulation, ISH) ( López
GR-RBPJ DBM (Dex NF12): ↓hes4 NCC domain at neural
notch1/
et al., 2005 ).
fold stage ( Glavic et al., 2004 ).
RBPJ
GR-RBPJ-Ank or GR-NICD1–22:
dll1 STU: ↓hes4 in NCC (neural plate stage) ( Vega-López
Dex, unstated stage :
et al., 2015 ).
↑ NCC hes4 domain (neural plate stage) ( Vega-López
et al., 2015 ).
Dex NF12:
↑ NCC hes4 domain (neural fold stage) ( Glavic
et al., 2004 ).
notch/
No regulation in NCC.
GR-RBPJ-Ank (Dex NF11): did not affect the NCC hes4 GR-RBPJ DBM (Dex NF11): did not affect the NCC hes4
RBPJ
domain at neural plate stage ( Nichane et al., 2008a ).
domain at neural plate stage ( Nichane et al., 2008a ).
(Continued)
hes4
hes3 hes2
hes1
Gene
Notch Signaling in Early Embryogenesis
TABLE 7.3
Experimental Evidence for the Responsiveness of hes1–7 and hey Genes to the Notch Pathway in Xenopus
No references were found for hes5.8, hes5.9, and hey2 regulation by the Notch pathway in Xenopus, and therefore they are not listed in this table. Abbreviations for Tables 7.3 to 7.12 : AP, anterior-posterior; aPM,
anterior prechordal mesoderm; ANB, anterior neural border; bHLH, basic helix-loop-helix; ChIP, chromatin immunoprecipitation; CHX, cycloheximide (an inhibitor of protein synthesis); Dex, dexamethasone;
DIMZ, dorsal involuting marginal zone; dll1 STU, antimorph of dll1, lacking the intracellular domain ( Chitnis et al., 1995 ); DML, dorsal midline; DMZ, dorsal marginal zone; DN, dominant-negative; DBM, DNA
binding mutant; DNIMZ, dorsal non-involuting marginal zone; E1A constructs, protein of interest fused to the activation domain of the human type 5 adenovirus E1a protein; EnR constructs, protein of interest fused
to the Drosophila Engrailed repressor domain; ER-constructs, hormone-inducible forms of proteins with nuclear functions under the control of the ligand-binding domain of the human estrogen receptor. These
recombinant fusion proteins translocate to the cell nucleus when estradiol (E2) is added to the culture medium at the desired NF stage; FP, f oor plate (ventral midline of the neural tube); GO, gastrula organizer;
GR-constructs, hormone-inducible forms of proteins with nuclear functions under the control of the ligand-binding domain of the human glucocorticoid receptor. These recombinant fusion proteins translocate to the
cell nucleus when Dex is added to the culture medium at the desired NF stage; GR- NICD1–22: hormone-inducible form of the X. laevis Notch1 intracellular domain ( Wettstein et al., 1997 ); HDAC, histone
deacetylase; HUA, hydroxyurea and aphidicolin (strong inhibitors of cell proliferation); ICD, intracellular domain; IMZ, involuting marginal zone; ISH, in situ hybridization; MHB, midbrain/hindbrain boundary;
MO, antisense morpholino oligonucleotide; NB, neural border; NCCs, neural crest cells; NF, Nieuwkoop and Faber stage of development in Xenopus; NICD, Notch intracellular domain (NICD constructs are
constitutively active); NIMZ, non-involuting marginal zone; notch1-ΔE, notch1 construct without most of the extracellular domain, constitutively active; pH3, phosphorylated form of histone H3 (marker of cell
proliferation); PN, primary neurogenesis; PPE, pre-placodal ectoderm; pPM, posterior prechordal mesoderm; PSM, presomitic mesoderm; RA, retinoic acid; RAR, retinoic acid receptor; RBPJ, recombination signal
binding protein for immunoglobulin kappa J region, transcription factor that mediates canonical Notch signaling; RBPJ-Ank: constitutively active form of the transcription factor RBPJ, consisting of the X. laevis
Notch1 ankyrin repeats fused to the C-terminus of X. laevis RBPJ ( Wettstein et al., 1997 ); RBPJ DBM, DNA binding mutant form of X. laevis RBPJ that binds to NICD but lacks the ability to bind target sites in the
DNA and acts as a dominant-negative protein by forming non-functional complexes ( Wettstein et al., 1997 ); sq, semiquantitative; TBD, tailbud region of the presomitic mesoderm; TF, transcription factor; TZ,
transition zone of the presomitic mesoderm; VMZ, ventral marginal zone; Δ, deletion; ↑up-regulation, expansion, or increase; ↓down-regulation, reduction, or decrease.
Regulated by
Regulation/Details
Gain-of-Function
Loss-of-Function
(Dominant-Negative/Antagonist/Morpholino)
dll1/
Positive in pronephros and neural plate.
GR-RBPJ-Ank, Dex NF18: ↑hes1 in pronephros ( Taelman RBPJ DBM :
↓ hes1 in pronephros ( Taelman et al., 2006 ).
notch/
et al., 2006 ).
dll1 STU :
↓hes1 in neural plate domains ( Yan
RBPJ
GR-RBPJ-Ank, Dex unstated stage : ↑hes1 neural plate
et al., 2009 ; Vega-López et al., 2015 ).
domains ( Vega-López et al., 2015 ).
notch1/
Positive in NB.
NICD1 or RBPJ-Ank : ectopic hes2 restricted to the lateral
RBPJ
border of the neural plate ( Sölter et al., 2006 ).
notch1
Positive.
NICD1: ↑hes3 (NF18, microarray) ( Vasiliu et al.,
2015 ).
dll1/
Positive in NB/NCC.
NICD1 : ↑NB hes4 domain (gastrulation, ISH) ( López
GR-RBPJ DBM (Dex NF12): ↓hes4 NCC domain at neural
notch1/
et al., 2005 ).
fold stage ( Glavic et al., 2004 ).
RBPJ
GR-RBPJ-Ank or GR-NICD1–22:
dll1 STU: ↓hes4 in NCC (neural plate stage) ( Vega-López
Dex, unstated stage :
et al., 2015 ).
↑ NCC hes4 domain (neural plate stage) ( Vega-López
et al., 2015 ).
Dex NF12:
↑ NCC hes4 domain (neural fold stage) ( Glavic
et al., 2004 ).
notch/
No regulation in NCC.
GR-RBPJ-Ank (Dex NF11): did not affect the NCC hes4 GR-RBPJ DBM (Dex NF11): did not affect the NCC hes4
RBPJ
domain at neural plate stage ( Nichane et al., 2008a ).
domain at neural plate stage ( Nichane et al., 2008a ).
(Continued)
hes4
hes3 hes2
hes1
Gene