Transcript Amylase Regulatory interactions during pancreatic development

Suc/Isom.
IFABP
Notch signaling
Exocrine Transcription
Intestinal Transcription
Amylase
Jagged1
Jagged2
Dll1
Gut
Gut
Wnt/b-cat.
?
Gut
Cdx1
MIST1
GATA4
Cdx2
?
Notch1
Gut
?
Ptf1a
nr5a2
Endoderm Establishment
Pancreas Determination
HNF1a
HNF4
HlxB9
?
Sox9
Via Sox17 or Mix?
SMAD2/SMAD4
/SMAD4
Endocrine fate Allocation
?
Six3
ENDODERM
PDX1MED
FoxA2
Ngn3-E2A
Eye
Via nkx2.2?
X.L
Nkx2.2
Activin or nrf
HNF1b
X.L
Sox17
HNF6
Eye
NeuroD-E2A
FGF10
Z.F
Z.F
Mixer/Bon
Hes1
?
Core Endodermal program
GATA6
Oct4
Notch2
Casanova
Nkx6.1
Indirectly
Cell
cycle
Exit
Prox1
Eye
Eye
COUP-TFII
Hex
Z.F
Pax6
Pax4
C/EBP-a
Nodal
Gut
Pbx1
Pancreas
Insulin
Gli2
SMAD1/SMAD4
/SMAD4/
HNF1a
PDX1HIGH
Pax4
FoxA2
FoxO1
Pax2
Eye
FoxA3
Glucagon
Brn4
Isl1
HNF4
LIVER TRANSCRIPTION
Also involving most members of
the core endodermal program
BMP
mafA < =? > L-Maf
Shh
Beta-cell Transcription
Symbols
Documented interaction, positive
Documented interaction, negative
Documented interaction, not in pancreas
Autoregulation
Suggested interaction, not proven
Extra-cellular signaling
Z.F
X.L
Hyperlink, review on subject
Link demonstrated in Zebrafish
Link demonstrated in Xenopus Laevis
Hyperlink, description of targeted mutation of gene
Comment on auto-regulation arrows:
Green: The gene acts by a self-sustainable mechanism – intrinsic stability of network
Red: The gene may act by a threshold mechanism – intrinsic instability of network
FoxA1
Alpha-cell Transcription
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Comment on targeted mutation links:
Studies of the genes by targeting mutations may have been performed by several independent groups, and several publications may
exist regarding a particular gene. Furthermore, independent targeting may have been performed, as is the case for e.g. Pdx1, HB9,
Ptf1a, NeuroD. Here, each link branches out only to one given study. Please consult the text for additional information to other
references having provided information about the role of the gene in pancreatic development using a targeted mutation approach.
Regulatory interactions during pancreatic development, obtained from Jan Jensen. Barbara Davis Center for Childhood Diabetes, U. Colorado Health Sciences Center.