Date of Award
Campus Access Dissertation
Doctor of Philosophy (PhD)
Biology/Molecular, Cellular, and Organismal Biology
Cell fate determination and growth regulation are key processes in organism development. These processes are tightly regulated by cell signaling pathways, such as the conserved Hippo pathway. It is well established that the Hippo pathway controls tissue growth through core kinase cascade in response to the upstream inputs. However, the mechanisms of the transcriptional and post-transcriptional regulation of the Hippo pathway in cell fate decisions and tissue growth are still not well understood. In this dissertation, I use Drosophila melanogaster as a model organism to investigate these mechanisms.
I uncovered a function of the Hippo pathway in cell fate decisions in the developing Drosophila eye, exerted through the interaction of the transcriptional coactivator Yorkie (Yki) with the transcriptional regulator Bonus (Bon), an ortholog of mammalian Transcriptional Intermediary Factor 1/tripartite motif (TIF1/TRIM) family proteins. Instead of controlling tissue growth, Yki and Bon promote epidermal and antennal fates at the expense of the eye fate. Proteomic, transcriptomic, and genetic analyses reveal that Yki and Bon control these cell fate decisions by recruiting transcriptional and post-transcriptional co-regulators, and by repressing Notch target genes and activating epidermal differentiation genes.
I also identified an RNA-binding protein Spenito (Nito), an ortholog of mammalian RNA binding motif protein 15/15B (RBM15/15B) and a component of the N6-methyladenosine (m6A) methyltransferase complex, as a novel interactor of Yki. I found that Nito suppresses the expression of canonical Yki target reporters and inhibits Yki-induced tissue overgrowth. Interestingly, this function involves another two accessory components of the m6A complex, Fl(2)d and Vir, but not the methyltransferases, suggesting a methyltransferase-independent function of these proteins in regulating the Hippo pathway in tissue growth.
Overall, this dissertation research expands our understanding of the functions and regulatory mechanisms in the Hippo pathway.
Zhao, Heya, "Control of Cell Fate Decisions and Tissue Growth by the Hippo Pathway" (2023). Graduate Doctoral Dissertations. 810.
Available for download on Sunday, June 01, 2025