Investigating a role for Myt1 kinase in the Drosophila intestinal epithelium

• Author / Creator

  Willms, Reegan J

• Myt1 kinase performs several functions during Drosophila development. Myt1 has firstly been described as a regulator of the G2/M DNA damage checkpoint in the developing wing disc. In addition, Myt1 has been shown to regulate several aspects of male and female gametogenesis, while also coordinating cell cycle exit of germline associated somatic cells. Many unknowns remain, however, including the mechanism by which Myt1 functions in somatic cells, as well as the degree to which this mechanism is conserved in other Drosophila tissues. Furthermore, a role for Myt1 in adult flies beyond gametogenesis has not yet been described. The Drosophila adult intestinal epithelium has been shown to possess a population of multipotent stem cells that give rise to differentiated epithelial cell types. Given that the majority of these intestinal stem cells proceed regularly through the mitotic cycle, I reasoned that Cdk1 inhibitory phosphorylation must be required to maintain intestinal stem cell homeostasis. Furthermore, these cells frequently produce transient daughter cells known as EBs that exit the mitotic cell cycle to produce absorptive enterocytes in a Notch dependent manner. This system, therefore, provides an excellent opportunity to investigate the formerly described regulatory roles of Myt1 in a previously unexplored setting. In this thesis, I examine the function of Myt1 in the adult fly intestine and provide evidence that Myt1 is an essential regulator of intestinal homeostasis. I demonstrate that Myt1 regulates cell division in the intestinal epithelium, and also show that it is required to promote mitotic cell cycle exit in EBs, a normally post-mitotic cell. Furthermore, I demonstrate that Myt1 activity in the Drosophila intestine is dependent on Cyclin A/Cdk1 and provide evidence that regulation by Myt1 occurs in G1 phase, a phase in which Myt1 activity has never before been described in vivo.

• Subjects / Keywords

  • Myt1
  • Cdk1
  • cell cycle
  • Drosophila
  • intestine

• Graduation date

  Spring 2019

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/r3-gr9t-gc90

• License

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