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Conditional expression of Spry1 in neural crest causes craniofacial and cardiac defects.

Yang X, Kilgallen S, Andreeva V, Spicer DB, Pinz I, Friesel R - BMC Dev. Biol. (2010)

Bottom Line: Spry1;Wnt1-Cre embryos die perinatally and exhibit facial clefting, cleft palate, cardiac and cranial nerve defects.These defects appear to be the result of decreased proliferation and increased apoptosis of neural crest and neural crest-derived cell populations.In addition, the domains of expression of several key transcription factors important to normal craniofacial and cardiac development including AP2, Msx2, Dlx5, and Dlx6 were reduced in Spry1;Wnt1-Cre transgenic embryos.

View Article: PubMed Central - HTML - PubMed

Affiliation: Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, ME 04074, USA.

ABSTRACT

Background: Growth factors and their receptors are mediators of organogenesis and must be tightly regulated in a temporal and spatial manner for proper tissue morphogenesis. Intracellular regulators of growth factor signaling pathways provide an additional level of control. Members of the Sprouty family negatively regulate receptor tyrosine kinase pathways in several developmental contexts. To gain insight into the role of Spry1 in neural crest development, we analyzed the developmental effects of conditional expression of Spry1 in neural crest-derived tissues.

Results: Here we report that conditional expression of Spry1 in neural crest cells causes defects in craniofacial and cardiac development in mice. Spry1;Wnt1-Cre embryos die perinatally and exhibit facial clefting, cleft palate, cardiac and cranial nerve defects. These defects appear to be the result of decreased proliferation and increased apoptosis of neural crest and neural crest-derived cell populations. In addition, the domains of expression of several key transcription factors important to normal craniofacial and cardiac development including AP2, Msx2, Dlx5, and Dlx6 were reduced in Spry1;Wnt1-Cre transgenic embryos.

Conclusion: Collectively, these data suggest that Spry1 is an important regulator of craniofacial and cardiac morphogenesis and perturbations in Spry1 levels may contribute to congenital disorders involving tissues of neural crest origin.

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The whole mount expression pattern of Spry1 in developing mouse embryos. (A) E8.0, (B) E8.5, (C) E9.0, (D) E9.5 and (E, F) E10. Spry1 is expressed in the primitive streak, brachial arches, midbrain-hindbrain boundary, lateral mesoderm and tail bud. E8.5 Spry1+/-LacZ embryos were stained with β-gal and sectioned through the plane indicated (G). β-gal staining is evident in the presumptive neural crest (H, arrowheads indicate the neural folds) and higher magnification (I).
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Figure 1: The whole mount expression pattern of Spry1 in developing mouse embryos. (A) E8.0, (B) E8.5, (C) E9.0, (D) E9.5 and (E, F) E10. Spry1 is expressed in the primitive streak, brachial arches, midbrain-hindbrain boundary, lateral mesoderm and tail bud. E8.5 Spry1+/-LacZ embryos were stained with β-gal and sectioned through the plane indicated (G). β-gal staining is evident in the presumptive neural crest (H, arrowheads indicate the neural folds) and higher magnification (I).

Mentions: We examined the expression Spry1 in mouse embryos from E8.0 to E10.0 using whole-mount in situ hybridization. In situ hybridization analysis at E8.0 revealed that Spry1 is highly expressed in the cranial neural folds and presomitic mesoderm (Figure 1A) and continues to be expressed in regions populated by cells of neural crest origin including the branchial arches 1, 2, and 3, the frontonasal process, the midbrain hindbrain boundary, as well as limb buds and presomitic mesoderm at E9.0 (Figure 1C). This pattern persists until about E10.0 (Figure 1E,F). These expression data are consistent with a previous report [14]. To gain additional insight into the pattern of embryonic Spry1 expression, we performed β-gal staining on Spry1lacZ/+ embryos at E8.5. A coronal section through the rostral region indicates β-gal staining in the presumptive neural crest (Figure 1H, I black arrowhead) as well as the underlying mesoderm (Figure 1I, red arrow).


Conditional expression of Spry1 in neural crest causes craniofacial and cardiac defects.

Yang X, Kilgallen S, Andreeva V, Spicer DB, Pinz I, Friesel R - BMC Dev. Biol. (2010)

The whole mount expression pattern of Spry1 in developing mouse embryos. (A) E8.0, (B) E8.5, (C) E9.0, (D) E9.5 and (E, F) E10. Spry1 is expressed in the primitive streak, brachial arches, midbrain-hindbrain boundary, lateral mesoderm and tail bud. E8.5 Spry1+/-LacZ embryos were stained with β-gal and sectioned through the plane indicated (G). β-gal staining is evident in the presumptive neural crest (H, arrowheads indicate the neural folds) and higher magnification (I).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2874773&req=5

Figure 1: The whole mount expression pattern of Spry1 in developing mouse embryos. (A) E8.0, (B) E8.5, (C) E9.0, (D) E9.5 and (E, F) E10. Spry1 is expressed in the primitive streak, brachial arches, midbrain-hindbrain boundary, lateral mesoderm and tail bud. E8.5 Spry1+/-LacZ embryos were stained with β-gal and sectioned through the plane indicated (G). β-gal staining is evident in the presumptive neural crest (H, arrowheads indicate the neural folds) and higher magnification (I).
Mentions: We examined the expression Spry1 in mouse embryos from E8.0 to E10.0 using whole-mount in situ hybridization. In situ hybridization analysis at E8.0 revealed that Spry1 is highly expressed in the cranial neural folds and presomitic mesoderm (Figure 1A) and continues to be expressed in regions populated by cells of neural crest origin including the branchial arches 1, 2, and 3, the frontonasal process, the midbrain hindbrain boundary, as well as limb buds and presomitic mesoderm at E9.0 (Figure 1C). This pattern persists until about E10.0 (Figure 1E,F). These expression data are consistent with a previous report [14]. To gain additional insight into the pattern of embryonic Spry1 expression, we performed β-gal staining on Spry1lacZ/+ embryos at E8.5. A coronal section through the rostral region indicates β-gal staining in the presumptive neural crest (Figure 1H, I black arrowhead) as well as the underlying mesoderm (Figure 1I, red arrow).

Bottom Line: Spry1;Wnt1-Cre embryos die perinatally and exhibit facial clefting, cleft palate, cardiac and cranial nerve defects.These defects appear to be the result of decreased proliferation and increased apoptosis of neural crest and neural crest-derived cell populations.In addition, the domains of expression of several key transcription factors important to normal craniofacial and cardiac development including AP2, Msx2, Dlx5, and Dlx6 were reduced in Spry1;Wnt1-Cre transgenic embryos.

View Article: PubMed Central - HTML - PubMed

Affiliation: Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, ME 04074, USA.

ABSTRACT

Background: Growth factors and their receptors are mediators of organogenesis and must be tightly regulated in a temporal and spatial manner for proper tissue morphogenesis. Intracellular regulators of growth factor signaling pathways provide an additional level of control. Members of the Sprouty family negatively regulate receptor tyrosine kinase pathways in several developmental contexts. To gain insight into the role of Spry1 in neural crest development, we analyzed the developmental effects of conditional expression of Spry1 in neural crest-derived tissues.

Results: Here we report that conditional expression of Spry1 in neural crest cells causes defects in craniofacial and cardiac development in mice. Spry1;Wnt1-Cre embryos die perinatally and exhibit facial clefting, cleft palate, cardiac and cranial nerve defects. These defects appear to be the result of decreased proliferation and increased apoptosis of neural crest and neural crest-derived cell populations. In addition, the domains of expression of several key transcription factors important to normal craniofacial and cardiac development including AP2, Msx2, Dlx5, and Dlx6 were reduced in Spry1;Wnt1-Cre transgenic embryos.

Conclusion: Collectively, these data suggest that Spry1 is an important regulator of craniofacial and cardiac morphogenesis and perturbations in Spry1 levels may contribute to congenital disorders involving tissues of neural crest origin.

Show MeSH
Related in: MedlinePlus