Teratogenic effects of the endothelin receptor antagonist L-753,037 in the rat

Spence, Stan; Anderson, Charles A.; Cukierski, Mark A.; Patrick, Darryl

doi:10.1016/s0890-6238(98)00064-1

Cited by 54 publications

(30 citation statements)

References 45 publications

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“…MO knockdown of Ednra1 alone disrupts jaw joints, while co-injection of MOs targeting both receptors eliminates ventral structures and phenocopies the suc;edn1 -/-mutant, indicating that the two receptor functions are partially redundant. These defects resemble loss-of-function mutations in Ednra in the mouse , and treatments with Ednra antagonists in both rat and chick embryos (Kempf et al, 1998;Spence et al, 1999). However, unlike the mouse we find no evidence for elevated apoptosis as a cause of the skeletal phenotype, and instead show that there are early defects in the specification of NC cells, similar to suc;edn1 -/-mutants, particularly in joint precursors.…”

Section: Discussionsupporting

confidence: 52%

Requirements for Endothelin type-A receptors and Endothelin-1 signaling in the facial ectoderm for the patterning of skeletogenic neural crest cells in zebrafish

et al. 2007

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Genetic studies in mice and zebrafish have revealed conserved requirements for Endothelin 1 (Edn1) signaling in craniofacial development. Edn1 acts through its cognate type-A receptor (Ednra) to promote ventral skeletal fates and lower-jaw formation. Here, we describe the isolation and characterization of two zebrafish ednra genes -ednra1 and ednra2 -both of which are expressed in skeletal progenitors in the embryonic neural crest. We show that they play partially redundant roles in lower-jaw formation and development of the jaw joint. Knockdown of Ednra1 leads to fusions between upper-and lower-jaw cartilages, whereas the combined loss of Ednra1 and Ednra2 eliminates the lower jaw, similar to edn1 -/-mutants. edn1 is expressed in pharyngeal arch ectoderm, mesoderm and endoderm. Tissue-mosaic studies indicate that, among these tissues, a crucial source of Edn1 is the surface ectoderm. This ectoderm also expresses ednrA1 in an edn1-dependent manner, suggesting that edn1 autoregulates its own expression. Collectively, our results indicate that Edn1 from the pharyngeal ectoderm signals through Ednra proteins to direct early dorsoventral patterning of the skeletogenic neural crest.

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Section: Discussionsupporting

confidence: 52%

Requirements for Endothelin type-A receptors and Endothelin-1 signaling in the facial ectoderm for the patterning of skeletogenic neural crest cells in zebrafish

et al. 2007

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“…Ednra signaling is crucial for NCC development in mouse , rat (Spence et al 1999), zebrafish (Miller et al 2000) and chick (Kempf et al 1998). We have clarified the function of Ednra receptor signaling in this study, illustrating that it does not appear to be required for mandible bone development after NCC patterning.…”

Section: Discussionmentioning

confidence: 99%

Deletion of the endothelin-A receptor gene within the developing mandible

et al. 2005

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Signaling from the endothelin-A (Ednra) receptor is responsible for initiating multiple signaling pathways within neural crest cells (NCCs). Loss of this initiation is presumably the basis for the craniofacial defects observed in Ednra −/− embryos. However, it is not known whether continued Ednra signaling in NCC derivatives is required for subsequent development of the lower jaw. To address this question, mice containing loxP recombination sequences flanking a portion of the Ednra gene were bred with transgenic mice that express Cre recombinase under control of a Dlx5/6 enhancer element. We find that while Ednra gene inactivation within the mandibular arch of these Ednra conditional knockout embryos is detectable by embryonic day (E) 10.5, mandibular archspecific gene expression is normal, as is overall mandible development. These results suggest that while Ednra receptor signaling is crucial for early NCC patterning, subsequent Ednra signaling is not essential for mandible bone development.

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“…migratory NC cell development (Clouthier et al, 1998;Clouthier et al, 2000;Ivey et al, 2003;Thomas et al, 1998). Ednra signaling during CNC cell development appears conserved among vertebrates, as pharmacological antagonism of Ednra in the rat (Spence et al, 1999) or chick (Kempf et al, 1998) results in similar craniofacial defects as those observed in Ednra -/-mice. Similarly, an edn1 mutation in zebrafish, termed sucker or suc/et1, results in disruption of most cartilages of the ventral (distal) jaw Miller and Kimmel, 2001;Miller et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Endothelin-A receptor-dependent and -independent signaling pathways in establishing mandibular identity

et al. 2004

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The lower jaw skeleton is derived from cephalic neural crest (CNC) cells that reside in the mandibular region of the first pharyngeal arch. Endothelin-A receptor (Ednra) signaling in crest cells is crucial for their development, as Ednra–/– mice are born with severe craniofacial defects resulting in neonatal lethality. In this study, we undertook a more detailed analysis of mandibular arch development in Ednra–/– embryos to better understand the cellular and molecular basis for these defects. We show that most lower jaw structures in Ednra–/– embryos undergo a homeotic transformation into maxillary-like structures similar to those observed in Dlx5/Dlx6–/– embryos, though lower incisors are still present in both mutant embryos. These structural changes are preceded by aberrant expansion of proximal first arch gene expression into the distal arch, in addition to the previously described loss of a Dlx6/Hand2 expression network. However, a small distal Hand2expression domain remains. Although this distal expression is not dependent on either Ednra or Dlx5/Dlx6 function, it may require one or more GATA factors. Using fate analysis, we show that these distal Hand2-positive cells probably contribute to lower incisor formation. Together, our results suggest that the establishment of a `mandibular identity' during lower jaw development requires both Ednra-dependent and -independent signaling pathways.

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Teratogenic effects of the endothelin receptor antagonist L-753,037 in the rat

Cited by 54 publications

References 45 publications

Requirements for Endothelin type-A receptors and Endothelin-1 signaling in the facial ectoderm for the patterning of skeletogenic neural crest cells in zebrafish

Requirements for Endothelin type-A receptors and Endothelin-1 signaling in the facial ectoderm for the patterning of skeletogenic neural crest cells in zebrafish

Deletion of the endothelin-A receptor gene within the developing mandible

Endothelin-A receptor-dependent and -independent signaling pathways in establishing mandibular identity

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