Endosome-Mediated Epithelial Remodeling Downstream of Hedgehog-Gli Is Required for Tracheoesophageal Separation

被引：31

作者：

Nasr, Talia ^{[1
,2
,3
]}

Mancini, Pamela ^{[1
,2
,5
]}

Rankin, Scott A. ^{[1
,2
]}

Edwards, Nicole A. ^{[1
,2
]}

Agricola, Zachary N. ^{[4
]}

Kenny, Alan P. ^{[4
]}

Kinney, Jessica L. ^{[1
,2
]}

Daniels, Keziah ^{[1
,2
]}

Vardanyan, Jon ^{[1
,2
]}

Han, Lu ^{[1
,2
,6
]}

Trisno, Stephen L. ^{[1
,2
,3
]}

Cha, Sang-Wook ^{[1
,2
,7
]}

Wells, James M. ^{[1
,2
,3
]}

Kofron, Matthew J. ^{[1
,2
,3
]}

Zorn, Aaron M. ^{[1
,2
,3
]}

机构：

[1] Cincinnati Childrens Hosp Med Ctr, Ctr Stem Cell & Organoid Med, CuSTOM, Div Dev Biol, Cincinnati, OH 45219 USA

[2] Cincinnati Childrens Hosp Med Ctr, Perinatal Inst, Cincinnati, OH 45219 USA

[3] Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati, OH 45219 USA

[4] Cincinnati Childrens Hosp Med Ctr, Div Neonatol & Pulm Biol, Cincinnati, OH 45219 USA

[5] Icahn Sch Med Mt Sinai, Dept Cell Dev & Regenerat Biol, New York, NY 10029 USA

[6] Med Coll South Carolina, Hollings Canc Ctr, Charleston, SC 29425 USA

[7] Univ Cent Missouri, Sch Nat Sci, Warrensburg, MO 64093 USA

来源：

DEVELOPMENTAL CELL | 2019年 / 51卷 / 06期

关键词：

SONIC HEDGEHOG; LUNG; TRACHEA; MALFORMATIONS; MORPHOGENESIS; ESOPHAGUS; PROTEINS; RAB11;

D O I：

10.1016/j.devcel.2019.11.003

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The trachea and esophagus arise from the separation of a common foregut tube during early fetal development. Mutations in key signaling pathways such as Hedgehog (HH)/Gli can disrupt tracheoesophageal (TE) morphogenesis and cause life-threatening birth defects (TEDs); however, the underlying cellular mechanisms are unknown. Here, we use mouse and Xenopus to define the HH/Gli-dependent processes orchestrating TE morphogenesis. We show that downstream of Gli the Foxf1+ splanchnic mesenchyme promotes medial constriction of the foregut at the boundary between the presumptive Sox2+ esophageal and Nkx2-1+ tracheal epithelium. We identify a unique boundary epithelium co-expressing Sox2 and Nkx2-1 that fuses to form a transient septum. Septum formation and resolution into distinct trachea and esophagus requires endosome-mediated epithelial remodeling involving the small GTPase Rab11 and localized extracellular matrix degradation. These are disrupted in Gli-deficient embryos. This work provides a new mechanistic framework for TE morphogenesis and informs the cellular basis of human TEDs.

引用

页码：665 / +

页数：16

共 32 条

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Kolterud, Asa
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Prakash, Ajay
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Schnell, Santiago
Gumucio, Deborah L.
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[32] Wang H., 2018, DEVELOPMENT, V145

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