Date of Award
Spring 2018
Degree Type
Thesis
Department
Biological Sciences
Director of Thesis
Shannon Davis
First Reader
Lydia Matesic
Second Reader
Lydia Matesic
Abstract
The mouse pituitary gland secretes hormones that regulate many physiological processes including growth, stress response, and reproduction. The canonical WNT signaling pathway, activation of which results in nuclear accumulation of β-CATENIN and transcription of target genes including LEF1, is crucial for proper development of the pituitary gland. Pituitary progenitors that lack β-CATENIN at embryonic day of development 8.5 (E8.5) cannot form three of the six cell types of the anterior pituitary that produce growth hormone (GH), thyroid stimulating hormone (TSH), and prolactin (PRL). Additionally, stimulating canonical WNT signaling through creation of degradation-resistant β-CATENIN at E9.5 causes pituitary tumors and results in a reduction in the number of GH and TSH secreting cells. However, if canonical WNT signaling is stimulated in differentiating pituitary cells at E14.5, there is no loss of hormone cell types or tumor formation, demonstrating that the timing of the signaling is critical. Based on these results we chose to activate canonical WNT signaling at E11.5 in pituitary progenitors by creating a degradation-resistant β-CATENIN using a Cre/loxP strategy to excise a portion of β-CATENIN exon 3 necessary for normal degradation. We found that activation of canonical WNT signaling at E11.5 resulted in hyperplastic pituitaries, increased epithelial-like tissue, and complete loss of all hormone-producing cell lineages. Our results demonstrate that proper regulation and timing of canonical WNT signaling during pituitary development is critical for proper differentiation of pituitary progenitors into hormone cell types.
First Page
1
Last Page
32
Recommended Citation
Coleman, Tanner F., "Stimulating Canonical WNT Signaling in Pituitary Progenitors Inhibits Differentiation of Hormone Cell Types" (2018). Senior Theses. 250.
https://scholarcommons.sc.edu/senior_theses/250
Rights
© 2018, Tanner F Coleman