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Dev Biol 2018 Feb 01;4341:121-132. doi: 10.1016/j.ydbio.2017.11.018.
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Timing is everything: Reiterative Wnt, BMP and RA signaling regulate developmental competence during endoderm organogenesis.

Rankin SA , McCracken KW , Luedeke DM , Han L , Wells JM , Shannon JM , Zorn AM .

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.

PubMed ID: 29217200
PMC ID: PMC5785443
Article link: Dev Biol
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: adm aldh1a2 bmp4 cdx2 ctnnb1 cyp26a1 dkk1 foxa1 foxe1 gata4 hhex nkx2-1 nog nsd1 odc1 pdx1 rdh10 satb2 sftpc sox17a sox2 sox9 stom tbx1 ventx1.2 ventx2.2 wnt3a
GO keywords: Wnt signaling pathway [+]
Antibodies: Ctnnb1 Ab2 GFP Ab20 Nkx2-1 Ab3 Sox2 Ab4

Article Images: [+] show captions
References [+] :
Bayha, Retinoic acid signaling organizes endodermal organ specification along the entire antero-posterior axis. 2009, Pubmed