RT Journal Article
SR Electronic
T1 Bidirectional Wnt signaling between endoderm and mesoderm confer tracheal identity in mouse and human
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 758235
DO 10.1101/758235
A1 Keishi Kishimoto
A1 Kana T. Furukawa
A1 Agustin Luz Madrigal
A1 Akira Yamaoka
A1 Chisa Matsuoka
A1 Masanobu Habu
A1 Cantas Alev
A1 Aaron M. Zorn
A1 Mitsuru Morimoto
YR 2020
UL http://biorxiv.org/content/early/2020/04/23/758235.abstract
AB The periodic cartilage and smooth muscle structures in mammalian trachea are derived from tracheal mesoderm, and tracheal malformations result in serious respiratory defects in neonates. Here we show that canonical Wnt signaling in mesoderm is critical to confer trachea mesenchymal identity in human and mouse. Loss of β-catenin in fetal mouse mesoderm caused loss of Tbx4+ tracheal mesoderm and tracheal cartilage agenesis. The Tbx4 expression relied on endodermal Wnt activity and its downstream Wnt ligand but independent of known Nkx2.1-mediated respiratory development, suggesting that bidirectional Wnt signaling between endoderm and mesoderm promotes trachea development. Repopulating in vivo model, activating Wnt, Bmp signaling in mouse embryonic stem cell (ESC)-derived lateral plate mesoderm (LPM) generated tracheal mesoderm containing chondrocytes and smooth muscle cells. For human ESC-derived LPM, SHH activation was required along with Wnt to generate proper tracheal mesoderm. Together, these findings may contribute to developing applications for human tracheal tissue repair.Competing Interest StatementThe authors have declared no competing interest.