Disruption of apoptosis and WNT signaling during limb morphogenesis by exogenous retinoic acid: a case study in Monodelphis domestica

Retinoic acid;limb development;morphogenesis;organogenesis;apoptosis;WNT signaling;Monodelphis domestica

Molineaux, Anna ; Sears ; Karen E.

关键词: Retinoic acid;    limb development;    morphogenesis;    organogenesis;    apoptosis;    WNT signaling;    Monodelphis domestica;   

Others  :  https://www.ideals.illinois.edu/bitstream/handle/2142/45313/Anna_Molineaux.pdf?sequence=1&isAllowed=y

美国|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

Retinoic Acid (RA) is a vitamin A derivative with severe teratogenic properties. RA is essential for normal limb development; but too much RA results in defects such as digit reduction and truncation of the limb. During normal limb morphogenesis, two signaling centers, the apical ectodermal ridge (AER) and the zone of polarizing activity (ZPA), regulate proper proximal-distal (PD) and anterior-posterior (AP) patterning of the limb, respectively. Despite exhaustive research, there is still no consensus as to how RA interacts with these signaling centers, or the other genes involved in the core-regulatory network for limb organogenesis. By manipulating forelimb growth in Monodelphis domestica, a novel model system for limb development, this study sheds new light on the mechanisms by which RA disrupts patterning of the AP and PD axes.Based on the results of this study, I propose that RA induces digit reduction by upregulating apoptotic events within the ZPA, while simultaneously downregulating SHH expression. Truncation of the limbs PD axis may be the result of the disruptive effects of RA on WNT signaling genes. Characterization of the interactions between RA and genes that regulate these developmental processes are described herein.