Role of Sonic hedgehog in the development of the trachea and oesophagus

Ioannides, Adonis S.; Henderson, Deborah J.; Spitz, Lewis; Copp, Andrew J.

doi:10.1053/jpsu.2003.50005

Cited by 69 publications

(66 citation statements)

References 15 publications

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“…The anal atresia in pigs documented by Van der Putte and Neeteson (Van der Putte and Neeteson, 1984) has been traced to a heritable mutation on chromosome 15 that maps near the location of Gli2 (Cassini et al, 2005). Both the Shh and Gli2/3 mouse mutants have been suggested as models of the VACTERL complex (Arsic et al, 2002;Kim et al, 2001;Mo et al, 2001), and ARMs caused by treatment with either retinoic acid or etretinate (a vitamin A derivative) produce ARM that resemble the phenotypes presented here (Dawrant et al, 2008;Ioannides et al, 2003;Kubota et al, 2000;Kubota et al, 1998;. A number of other mutations, such as ephrin B2 (Efnb2 -Mouse Genome Informatics), Trp63, Bmp7 and Fgf10, also result in anorectal and urogenital malformations, and in light of our findings it will be interesting to determine whether these pathways, as well as environmental contaminants, result in coordinated malformations of anorectal and urogenital organs because of a shared temporal window of sensitivity.…”

Section: A Novel Role For Surface Ectoderm In Hypospadiasmentioning

confidence: 56%

Multiphasic and tissue-specific roles of sonic hedgehog in cloacal septation and external genitalia development

et al. 2009

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Malformations of the external genitalia are among the most common congenital anomalies in humans. The urogenital and anorectal sinuses develop from the embryonic cloaca, and the penis and clitoris develop from the genital tubercle. Within the genital tubercle, the endodermally derived urethral epithelium functions as an organizer and expresses sonic hedgehog (Shh). Shh knockout mice lack external genitalia and have a persistent cloaca. This identified an early requirement for Shh, but precluded analysis of its later role in the genital tubercle. We conducted temporally controlled deletions of Shh and report that Shh is required continuously through the onset of sexual differentiation. Shh function is divisible into two temporal phases; an anogenital phase, during which Shh regulates outgrowth and patterning of the genital tubercle and septation of the cloaca, and a later external genital phase, during which Shh regulates urethral tube closure. Disruption of Shh function during the anogenital phase causes coordinated anorectal and genitourinary malformations, whereas inactivation during the external genital phase causes hypospadias. Shh directs cloacal septation by promoting cell proliferation in adjacent urorectal septum mesenchyme. Additionally, conditional inactivation of smoothened in the genital ectoderm and cloacal/urethral endoderm shows that the ectoderm is a direct target of Shh and is required for urethral tube closure, highlighting a novel role for genital ectoderm in urethragenesis. Identification of the stages during which disruption of Shh results in either isolated or coordinated malformations of anorectal and external genital organs provides a new tool for investigating the etiology of anogenital malformations in humans.

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Section: A Novel Role For Surface Ectoderm In Hypospadiasmentioning

confidence: 56%

Multiphasic and tissue-specific roles of sonic hedgehog in cloacal septation and external genitalia development

et al. 2009

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“…Other studies investigating the nature of oesophageal and tracheal deformities in Adriamycin exposed embryos have suggested that changes in Shh expression in the foregut itself are responsible for these defects (Arsic et al, 2004, Arsic et al, 2003, Ioannides et al, 2003 and oesophageal development is also perturbed in Hh deficient zebrafish embryos (Wallace and Pack, 2003). By analogy, it seems plausible changes in Hh expression in the posterior gut underlies the teratogen induced ARMs .…”

Section: High Levels Of Hh Activity Are Necessary For Correct Anorectmentioning

confidence: 98%

Hedgehog signalling is required for cloacal development in the zebrafish embryo

Parkin¹,

Allen²,

Ingham³

2009

Int. J. Dev. Biol.

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The Hedgehog (Hh) family of signalling molecules is essential for a wide range of developmental processes. Mammalian studies have implicated the Hedgehog pathway in the aetiology of anorectal malformations (ARMs), relatively common congenital anomalies caused by failures in the development of the cloaca. In this study we demonstrate that Hh signalling is absolutely required for the formation of the zebrafish cloaca and that the severity of the posterior gut abnormalities induced by a reduction in Hh activity is dependent on the levels of Hh signal transduction. The complete loss of all Hh activity results in the most severe defects and the critical period for Hh activity is between 34 and 74 hours post fertilisation. Using a range of mutant genotypes that cause notochord and floorplate abnormalities, we show that the source of the Hh signals required for posterior gut formation is the endoderm and not the notochord, as previously postulated in mammalian models of ARMs. We show that Adriamycin, a drug known to cause ARMs in rat, but not chick embryos, has no effect on the development of the zebrafish gastrointestinal tract. These studies establish the zebrafish as a model for ARMs, and for the elucidation of other pathways involved in hindgut developmental processes.

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“…25 The study was prompted by observations that such human congenital pulmonary malformations as lung hypoplasia, tracheoesophageal fistula, and esophageal atresia may be attributed to defective SHH signaling. [26][27][28][29] Taken together, these studies illustrate how molecular technology may be used to identify the timing of PNEC fate restriction and lineage relationships during morphogenesis. 17 In the immature, developing lung markers of NE differentiation are co-expressed with the epithelial markers before they are restricted to specific PNECs, suggesting a common cellular origin for airway cells.…”

mentioning

confidence: 88%

Functional facets of the pulmonary neuroendocrine system

Linnoila

2006

Laboratory Investigation

178

143

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Pulmonary neuroendocrine cells (PNECs) have been around for 60 years in the scientific literature, although phylogenetically they are ancient. Their traditionally ascribed functions include chemoreception and regulation of lung maturation and growth. There is recent evidence that neuroendocrine (NE) differentiation in the lung is regulated by genes and pathways that are conserved in the development of the nervous system from Drosophila to humans (such as achaete-scute homolog-1), or implicated in the carcinogenesis of the nervous or NE system (such as the retinoblastoma tumor suppressor gene). In addition, complex neural networks are in place to regulate chemosensory and other functions. Even solitary PNECs appear to be innervated. For the first time ever, we have mouse models for lung NE carcinomas, including the most common and virulent small cell lung carcinoma. Moreover, PNECs may be important for inflammatory responses, and pivotal for lung stem cell niches. These discoveries signify an exciting new era for PNECs and are likely to have therapeutic and diagnostic applications.

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Role of Sonic hedgehog in the development of the trachea and oesophagus

Cited by 69 publications

References 15 publications

Multiphasic and tissue-specific roles of sonic hedgehog in cloacal septation and external genitalia development

Multiphasic and tissue-specific roles of sonic hedgehog in cloacal septation and external genitalia development

Hedgehog signalling is required for cloacal development in the zebrafish embryo

Functional facets of the pulmonary neuroendocrine system

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