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. 2017 Mar 24;7:389. doi: 10.1038/s41598-017-00334-1

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© The Author(s) 2017

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Malformations observed in embryos from diabetic pregnancies after 10.5 days of gestation. (A,B) Examples of caudal malformations observed in wild type embryos from diabetic pregnancies. Tail flexion defects are indicated by arrowheads. (D,E) Examples of cranial malformations observed in heterozygote Alx3-deficient embryos from diabetic pregnancies. These include defects of the rostral mesenchyme affecting midline closure at the level of the forehead (D, arrowheads), defects at the level of the mesencephalic vesicles (D, arrows) and defects of facial mesenchyme expansion (E, arrowheads) affecting the development of the telencephalic vesicles (E, arrows). (G,H) Examples of severe malformations found in Alx3-null embryos developing in diabetic mothers. Malformations affected several embryonic regions including the forehead mesenchyme, the branchial arches and the cranial neural tube (G), or were restricted to severe craniofacial and cranial neural tube closure defects (H, arrows). Arrowheads indicate open neural folds. (C,F and I) depict normal wild type embryos for comparisons. Scale bars represent 1 mm in all cases except in G (1.5 mm). Abbreviations: ba, Branchial arches; FLB, Forelimb bud; HLB, Hind limb bud; m, Mesencephalon; r, Rhombencephalon; t, Telencephalic vesicles.