Tracheal Agenesis: A Rare Disease with Unique Airway Considerations

Saleeby, Manhal G.; Vustar, Mirjana; Algren, John T.

doi:10.1213/01.ane.0000066358.67483.4d

Cited by 12 publications

(11 citation statements)

References 4 publications

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“…A putative mechanism for the role of BMP signaling in congenital foregut defects Tracheal agenesis is a rare, but often fatal, birth defect, the etiology of which is currently unknown (Heimann et al, 2007;Saleeby et al, 2003). Intriguingly, the phenotypes of Bmpr1a;b and conditional Bmp4 mutant mice resemble that of individuals suffering from this defect.…”

Section: Bmpr1a;b Maintain Respiratory Fate Through Repression Of Sox2mentioning

confidence: 99%

Signaling through BMP receptors promotes respiratory identity in the foregut via repression of Sox2

et al. 2011

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SUMMARYThe mammalian foregut gives rise to the dorsally located esophagus and stomach and the ventrally located trachea and lung. Proper patterning and morphogenesis of the common foregut tube and its derived organs is essential for viability of the organism at birth. Here, we show that conditional inactivation of BMP type I receptor genes Bmpr1a and Bmpr1b (Bmpr1a;b) in the ventral endoderm leads to tracheal agenesis and ectopic primary bronchi. Molecular analyses of these mutants reveal a reduction of ventral endoderm marker NKX2-1 and an expansion of dorsal markers SOX2 and P63 into the prospective trachea and primary bronchi. Subsequent genetic experiments show that activation of canonical WNT signaling, previously shown to induce ectopic respiratory fate in otherwise wild-type mice, is incapable of promoting respiratory fate in the absence of Bmpr1a;b. Furthermore, we find that inactivation of Sox2 in Bmpr1a;b mutants does not suppress ectopic lung budding but does rescue trachea formation and NKX2-1 expression. Together, our data suggest that signaling through BMPR1A;B performs at least two roles in early respiratory development: first, it promotes tracheal formation through repression of Sox2; and second, it restricts the site of lung bud initiation.

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Section: Bmpr1a;b Maintain Respiratory Fate Through Repression Of Sox2mentioning

confidence: 99%

Signaling through BMP receptors promotes respiratory identity in the foregut via repression of Sox2

et al. 2011

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“…It is often associated with a wide variety of other congenital anomalies of the heart, genitourinary, gastrointestinal, pulmonary and central nervous system but specific etiologies have not been identified (Evans et al, 1999; Faro et al, 1979; Kerschner and Klotch, 1997; Lander et al, 2004; Saleeby et al, 2003; Sparey et al, 2000; Wei et al, 2003). The Floyd anatomical classification describes three types of TA (Fig.…”

Section: Introductionmentioning

confidence: 99%

Bmp4 is required for tracheal formation: A novel mouse model for tracheal agenesis

Jack

Manley

et al. 2008

Developmental Biology

111

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Tracheal agenesis/atresia (TA) is a rare but fatal congenital disease in which the breathing tube fails to grow. The etiology of this serious condition remains largely unknown. We found that Bmp signaling is prominently present in the anterior foregut where the tracheal primordium originates and targeted ablation of Bmp4 (Bmp4cko) resulted in a loss-of-trachea phenotype that closely resembles the Floyd type II pathology, the most common form of TA in humans. In Bmp4cko embryos, tracheal specification was not affected, however, its outgrowth was severely impaired due to reduced epithelial and mesenchymal proliferation. In agreement, we also observed significant reduction in the expression of Cyclin D1, a key cell cycle regulator associated with cellular proliferation. However, the proliferative effect of Bmp signaling appears to be independent of Wnt signaling. Interestingly, we found significantly reduced expression of activated extracellular signal-regulated kinase (Erk) in the Bmp4cko ventral foregut, suggesting that Bmp signaling promotes Erk phosphorylation which has been associated with cellular proliferation. This study provides the first evidence linking Bmp signaling to tracheal formation by regulating the proliferative response of the anterior ventral foregut. Our finding sheds light on human tracheal malformations by providing a novel mouse model implicating Bmp signaling, non-canonical Erk activation and cellular proliferation.

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“…In the absence of communication with the esophagus, TA becomes an even more devastating malformation. Such a case can be ventilated only with surgical approach similarly to laryngeal atresia [3]. Tracheal agenesis and esophageal atresia in rats have been recently associated with Nog, a gene encoding a bone morphogenetic protein antagonist [6].…”

Section: Discussionmentioning

confidence: 99%

“…An ideal surgical therapy is still not defined [1], and available guidelines from the Neonatal Resuscitation Program do not provide any recommendation about such cases [2]. Nevertheless, most TA babies could temporarily be ventilated through a tracheoesophageal fistula by insertion of an endotracheal tube (ETT) in the esophagus [1,3]. We report an exceptional case of TA without communication with the esophagus in which surgical tracheotomy was performed.…”

mentioning

confidence: 99%

Tracheal agenesis without esophageal fistula: genetic, resuscitative, and pathological issues

Luca

Carolis

Capelli

et al. 2008

Journal of Pediatric Surgery

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Tracheal Agenesis: A Rare Disease with Unique Airway Considerations

Cited by 12 publications

References 4 publications

Signaling through BMP receptors promotes respiratory identity in the foregut via repression of Sox2

Signaling through BMP receptors promotes respiratory identity in the foregut via repression of Sox2

Bmp4 is required for tracheal formation: A novel mouse model for tracheal agenesis

Tracheal agenesis without esophageal fistula: genetic, resuscitative, and pathological issues

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