Morphogenesis of the trachea and esophagus: current players and new roles for noggin and Bmps

doi:10.1111/j.1432-0436.2006.00096.x

Differentiation

Volume 74, Issue 7, September 2006, Pages 422-437

https://doi.org/10.1111/j.1432-0436.2006.00096.x Get rights and content

Abstract

The development of the anterior foregut of the mammalian embryo involves changes in the behavior of both the epithelial endoderm and the adjacent mesoderm. Morphogenetic processes that occur include the extrusion of midline notochord cells from the epithelial definitive endoderm, the folding of the endoderm into a foregut tube, and the subsequent separation of the foregut tube into trachea and esophagus. Defects in foregut morphogenesis underlie the constellation of human birth defects known as esophageal atresia (EA) and tracheoesophageal fistula (TEF). Here, we review what is known about the cellular events in foregut morphogenesis and the gene mutations associated with EA and TEF in mice and humans. We present new evidence that about 70% of mouse embryos homozygous null for Nog, the gene encoding noggin, a bone morphogenetic protein (Bmp) antagonist, have EA/TEF as well as defects in lung branching. This phenotype appears to correlate with abnormal morphogenesis of the notochord and defects in its separation from the definitive endoderm. The abnormalities in foregut and lung morphogenesis of Nog null mutant can be rescued by reducing the gene dose of Bmp4 by 50%. This suggests that normal foregut morphogenesis requires that the level of Bmp4 activity is carefully controlled by means of antagonists such as noggin. Several mechanisms are suggested for how Bmps normally function, including by regulating the intercellular adhesion and behavior of notochord and foregut endoderm cells. Future research must determine how Noggin/Bmp antagonism fits into the network of other factors known to regulate tracheal and esophagus development, both in mouse or humans.

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¹: Present address: Department of Biology, Duke University, Durham, NC, U.S.A.

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ORIGINAL ARTICLEMorphogenesis of the trachea and esophagus: current players and new roles for noggin and Bmps

Abstract

Curr Opin Genet Dev

J Pediatr Surg

Dev Biol

Dev Biol

J Pediatr Surg

Dev Biol

Cell

Cell

J Pediatr Surg

Dev Biol

J Pediatr Surg

J Pediatr Surg

Semin Pediatr Surg

Dev Biol

Dev Biol

J Pediatr Surg

Curr Opin Genet Dev

Dev Biol

J Pediatr Surg

Hedgehog in the human: a possible explanation for the VATER association

J Paediatr Child Health

The organizer factors Chordin and Noggin are required for mouse forebrain development

Nature

The role of chordin/Bmp signals in mammalian pharyngeal development and DiGeorge syndrome

Development

The development of the proximal oesophageal pouch in the adriamycin rat model of oesophageal atresia with tracheo-oesophageal fistula

Pediatr Surg Int

Involvement of Sonic hedgehog (Shh) in mouse embryonic lung growth and morphogenesis

Development

Regulation of early lung morphogenesis: questions, facts and controversies

Development

Esophageal atresia and tracheoesophageal fistula

Am Fam Phys

The hedgehog signaling network

Am J Med Genet A

X-linked Opitz syndrome: novel mutations in the MID1 gene and redefinition of the clinical spectrum

Am J Med Genet A

Microdeletion 22q11 and oesophageal atresia

J Med Genet

Overlapping expression domains of bone morphogenetic protein family members potentially account for limited tissue defects in BMP7 deficient embryos

Dev Dynam

Genetics and developmental biology of oesophageal atresia and tracheo-oesophageal fistula: lessons from mice relevant for paediatric surgeons

Pediatr Surg Int

Extrusion and death of DPP/BMP-compromised epithelial cells in the developing Drosophila wing

Science

Heterozygous mutations in the gene encoding noggin affect human joint morphogenesis

Nat Genet

ORIGINAL ARTICLE
Morphogenesis of the trachea and esophagus: current players and new roles for noggin and Bmps