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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 How to use this file: 1. Download file to disk. 2. Open File by double clicking. Select “slideshow” option in PowerPoint (PC: press F5). Within the slideshow, point-and-click on arrow, gene, or symbol for exiting to hyperlinked information. Hyperlink information will display when hovering over symbol. Clicking within non-linked areas will terminate the slideshow. Press F5 to resume slideshow. For best results, a 17’’ screen, or larger, is recommended. 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.