Notch signaling
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Notch signaling. Exocrine Transcription. Intestinal Transcription. Suc/Isom. Amylase. IFABP. Jagged1. Jagged2. Dll1. Gut. ?. Gut. Gut. MIST1. Wnt /b- cat. Cdx1. GATA4. ?. Notch1. Notch2. Cdx2. Gut. ?. Ptf1a. Hes1. nr5a2. ?. Core Endodermal program.

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Presentation Transcript

Notch signaling

Exocrine Transcription

Intestinal Transcription

Suc/Isom.

Amylase

IFABP

Jagged1

Jagged2

Dll1

Gut

?

Gut

Gut

MIST1

Wnt/b-cat.

Cdx1

GATA4

?

Notch1

Notch2

Cdx2

Gut

?

Ptf1a

Hes1

nr5a2

?

Core Endodermal program

Pancreas Determination

Endocrine fate Allocation

Endoderm Establishment

GATA6

Oct4

HNF1a

HNF4

HlxB9

?

Sox9

?

Via Sox17 or Mix?

Six3

ENDODERM

SMAD2/SMAD4

/SMAD4

Ngn3-E2A

FoxA2

PDX1MED

Eye

Via nkx2.2?

X.L

Nkx2.2

Activin or nrf

Cell

cycle

Exit

HNF1b

HNF6

X.L

Eye

Sox17

NeuroD-E2A

Prox1

FGF10

Indirectly

Z.F

Eye

Nkx6.1

Z.F

Eye

COUP-TFII

Mixer/Bon

Casanova

Hex

Z.F

Pax6

Pax4

Pax2

C/EBP-a

Nodal

Gut

Pbx1

HNF1a

Pax4

Pancreas

FoxA2

Insulin

PDX1HIGH

FoxA3

Brn4

Glucagon

Eye

Gli2

SMAD1/SMAD4

/SMAD4/

Isl1

FoxO1

HNF4

LIVER TRANSCRIPTION

FoxA1

BMP

mafA < =? >

L-Maf

Also involving most members of the core endodermal program

Shh

Beta-cell Transcription

Alpha-cell Transcription

Symbols

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Documented interaction, positive

Hyperlink, review on subject

Documented interaction, negative

Link demonstrated in Zebrafish

Z.F

Documented interaction, not in pancreas

Link demonstrated in Xenopus Laevis

X.L

Autoregulation

Hyperlink, description of targeted mutation of gene

Suggested interaction, not proven

Extra-cellular signaling

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

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.


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