Timing is everything: Reiterative Wnt, BMP and RA signaling regulate developmental competence during endoderm organogenesis
| Autor: | John M. Shannon, Scott A. Rankin, Kyle W. McCracken, David M. Luedeke, Lu Han, James M. Wells, Aaron M. Zorn |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Organ induction animal structures Organogenesis Human Embryonic Stem Cells Tretinoin Biology Xenopus Proteins Article 03 medical and health sciences Mice Xenopus laevis Species Specificity Somitogenesis medicine Animals Humans Molecular Biology Endoderm Wnt signaling pathway Mouse Embryonic Stem Cells Cell Biology Cell biology Gastrulation Wnt Proteins Somite 030104 developmental biology medicine.anatomical_structure Somites embryonic structures Bone Morphogenetic Proteins Lung induction Developmental Biology |
| Popis: | A small number of signaling pathways are used repeatedly during organogenesis, and they can have drastically different effects on the same population of cells depending on the embryonic stage. How cellular competence changes over developmental time is not well understood. Here we used Xenopus, mouse, and human pluripotent stem cells to investigate how the temporal sequence of Wnt, BMP, and retinoic acid (RA) signals regulates endoderm developmental competence and organ induction, focusing on respiratory fate. While Nkx2-1+ lung fate is not induced until late somitogenesis stages, here we show that lung competence is restricted by the gastrula stage as a result of Wnt and BMP-dependent anterior-posterior (A-P) patterning. These early Wnt and BMP signals make posterior endoderm refractory to subsequent RA/Wnt/BMP-dependent lung induction. We further mapped how RA modulates the response to Wnt and BMP in a temporal specific manner. In the gastrula RA promotes posterior identity, however in early somite stages of development RA regulates respiratory versus pharyngeal potential in anterior endoderm and midgut versus hindgut potential in posterior endoderm. Together our data suggest a dynamic and conserved response of vertebrate endoderm during organogenesis, wherein early Wnt/BMP/RA impacts how cells respond to later Wnt/BMP/RA signals, illustrating how reiterative combinatorial signaling can regulate both developmental competence and subsequent fate specification. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|