A multi-modal investigation of the developmental origins of congenital heart defects in avian embryos Public Deposited

Maternal conditions that disrupt the normal embryonic environment during heart development can lead to structural defects in the heart, ultimately compromising the heart’s function and leading to increased morbidity and mortality. Avian models of cardiovascular development have played a key role in elucidating the mechanisms by which congenital heart defects form during critical periods of early heart development. However, current avian models are restricted to narrow developmental windows, thereby limiting one’s ability to study the manifestation of cardiac defects over a larger, more complete timescale. The work presented in this thesis uses novel techniques in an avian model coupled with multiscale imaging modalities to study how transient interventions during early heart formation affect the overall development of the heart. Specifically, we employ a combination of 3D electron microscopy, light microscopy, and micro-computed tomography to understand how pharmacological or surgical interventions performed during tubular heart stages affect both early- and late-stages of cardiac development. Overall,
our studies revealed unreported cardiac malformation phenotypes in response to early interventions as well as accompanying ultrastructural changes in cardiac tissues. Furthermore, the models and methods presented here provide a framework for a comprehensive multiscale developmental analysis that can potentially be applied to other organs in the chick, and adapted for use in other small animal models.

  • https://doi.org/10.6083/2b88qc733
  • rykiel.graham.2019.pdf
Publication Date
  • 2019
Document type