User:Kukam001/sandbox

Thalidomide is a teratogen known to be significantly detrimental to the development of certain body parts and organs in the body such as the eyes or the heart. During embryogenesis it is observed that many different organisms experience different impacts of teratogens on organ morphogenesis and development overall. One of these organisms that are popular to study the malformations created by thalidomide are chick embryos. It is observed that thalidomide induces limb outgrowth deformities through inducing oxidative stress and thereby enhancing genetic signaling through irregular expression of  bone morphogenic proteins, Bmp. According to a study that was performed in 2007, the results revealed that with the increased oxidative stress thalidomide promotes, the up-regulation of the Bmp target gene and Wnt antagonist (Dkk1) this in turn inhibited canonical Wnt/B-catenin signaling and an increase in cell death was observed. The thalidomide induced cell death was significantly reduced when the introduction of inhibitors against Bmp, Dkk1 (Wnt antagonist), and Gsk3B (B-catenin antagonist) was administered into the chick embryos and cell death of the limb tissue was decreased. These results helped to conclude that these three pathways significantly impacted by thalidomide for chick limb development and that the teratogenic outcomes of the limb development deficiencies thalidomide creates can be reversed if these three pathways are inhibited.

Retinoic acid (RA) is significant in embryonic development. It induces the function of limb patterning of a developing embryo in species such as mice and other vertebrate limbs For example during the process of regenerating a newt limb an increased amount of RA moves the limb more proximal to the distal blastoma and the extent of the proximalization of the limb increases with the amount of RA present during the regeneration process. A study looked at the RA activity intracellularly in mice in relation to human regulating CYP26 enzymes which play a critical role in metabolizing RA. This study also helps to reveal that RA is significant in various aspects of limb development in an embryo, however irregular control or excess amounts of RA can have teratogenic impacts causing malformations of limb development. They looked specifically at CYP26B1 which is highly expressed in regions of limb development in mice. The lack of CYP26B1 was shown to cause a spread of RA signal towards the distal section of the limb causing proximodistal patterning irregularities of the limb. Not only did it show spreading of RA but a deficiency in the CYP26B1 also showed an induced apoptosis effect in the developing mouse limb but delayed chondrocyte maturation, which are cells that secrete a cartilage matrix which is significant for limb structure. They also looked at what happened to development of the limbs in wild type mice, that are mice with no CYP26B1 deficiencies, but which had an excess amount of RA present in the embryo. The results showed a similar impact to limb patterning if the mice did have the CYP26B1 deficiency meaning that there was still a proximal distal patterning deficiency observed when excess RA was present. This then concludes that RA plays the role of a morphogen to identify proximal distal patterning of limb development in mice embryos and that CYP26B1 is significant to prevent apoptosis of those limb tissues to further proper development of mice limbs in vivo.