| Summary: | <p>My research focuses on the role of ASPP2 (Apoptosis-stimulating of p53 protein 2, encoded by the TP53BP2 gene) during early post-implantation development. ASPP2 has multiple important biological functions, including roles in the control of cell polarity, tight junction formation, cell proliferation, differentiation and apoptosis.</p>
<p>To study the molecular basis of ASPP2 function in post-implantation development, I generated a mouse line in which exon 4 of ASPP2 is flanked by LoxP sites. Using genetic crossings, this allowed me to generate various mouse lines that were used to study the function of ASPP2 in the whole embryo and in specific tissues.</p>
<p>My results indicate that gastrulation is able to proceed in ASPP2-/- embryos – all 3 germ layers appear to form correctly. However, the embryo becomes progressively more disordered as development proceeds, resulting in embryonic lethality by E9.5. Somites are present at E8.5 and E9.5, showing that mesoderm-derived structures can form. The somites, however, are smaller than their wildtype counterparts. Additionally, instead of the normal structure of a single layer of somitic cells surrounding a central cavity, the somites have a disorganised structure with multiple cell layers and often lack a cavity.</p>
<p>Heart formation is also affected in these mutant embryos. By E9.5, there is no heart structure, with the absence of a beating heart. I crossed the ASPP2flox/flox mouse line to a line expressing CRE under the Mesp1 promoter, which controls early cardiac progenitor formation. These mice developed normal hearts at E8.5 and E9.5, implying that the perturbation in cardiac development is a secondary defect, likely caused by disturbances to the surrounding tissues meaning that the cardiac progenitors do not receive the signals they require to continue developing.</p>
<p>Thus, my research has indicated that ASPP2 is essential for post-implantation embryonic development. The mesoderm initially forms correctly but as the embryo continues to develop, the mesoderm-derived somites become disrupted, indicating a role for ASPP2 in regulating the epithelial architecture of the somites. Similarly, as seen in the heart, the disorganisation of structures leads to secondary defects later in development, ultimately resulting in embryonic lethality. These results demonstrate the importance of ASPP2 and shed light on some of the functions that it may play in development.</p>
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