상세정보
Export to Refworks부가기능
Defining the Molecular Pathways that Regulate Endoreplication
상세 프로파일
| 자료유형 | 학위논문 |
|---|---|
| 서명/저자사항 | Defining the Molecular Pathways that Regulate Endoreplication. |
| 개인저자 | Rotelli, Michael D. |
| 단체저자명 | Indiana University. Biology. |
| 발행사항 | [S.l.]: Indiana University., 2019. |
| 발행사항 | Ann Arbor: ProQuest Dissertations & Theses, 2019. |
| 형태사항 | 243 p. |
| 기본자료 저록 | Dissertations Abstracts International 81-04B. Dissertation Abstract International |
| ISBN | 9781687903662 |
| 학위논문주기 | Thesis (Ph.D.)--Indiana University, 2019. |
| 일반주기 |
Source: Dissertations Abstracts International, Volume: 81-04, Section: B.
Includes supplementary digital materials. Advisor: Calvi, Brian R. |
| 이용제한사항 | This item must not be sold to any third party vendors. |
| 요약 | Endoreplication is a cell cycle variant during which cells duplicate their genome but do not divide. This results in large polyploid cells and serves as an alternative to mitosis for tissue growth. Endoreplication is highly conserved and contributes to the development and function of a diverse array of tissues in many eukaryotes. Moreover, cells can be induced into endoreplication (iEC-Induced Endoreplicating Cell) through various physiological stressors, including wounding and cancer. However, the precise mechanisms that regulate the switch from a mitotic cycle to an endoreplication cycle are not completely understood. I have studied induced endoreplication in Drosophila to delineate the genetic pathway(s) involved in the switch from mitotic cycles to endoreplication cycles.Previous work has shown that genetic ablation of Cyclin A is sufficient to induce endoreplication. Here, we show that knockdown of the transcription factor Myb, as well as its transcriptional target, Aurora B, are also sufficient to induce endoreplication. Comparing the transcriptomes of S2 cell iECs (CycA RNAi and Myb RNAi iECs) and Developmental Endoreplicating Cells (devECs) from salivary glands by RNA-seq has revealed that these endoreplicating cells share decreased expression of a vast number of genes. Interestingly, while devECs and Cyclin A-RNAi iECs have reduced expression of E2F1 transcriptional targets, all three types of ECs have reduced expression of Myb transcriptional targets. Furthermore, many of these Myb genes that are downregulated in iECs and devECs are integral for mitosis. Together these data show that the status of a CycA-MMB- Aurora B network is crucial for the decision to either commit to mitosis or switch to endoreplication cycles. These findings have broader relevance to understanding the contribution of these variant polyploid cycles to development, tissue regeneration, and cancer.We also performed an unbiased screen in order to identify novel regulators of tissue growth in the adult wing in Drosophila. We used the lines generated by the Transgenic RNAi Project to knockdown over 5000 individual genes. These experiments implicated several genes, with poorly understood functions, in the development of the adult wing, and likely tissue growth in general. These studies have expanded our knowledge of how cells switch from mitosis to endoreplication, and additionally identified novel regulators of tissue growth in the Drosophila wing |
| 일반주제명 | Cellular biology. Genetics. Molecular biology. |
| 언어 | 영어 |
| 바로가기 | 
: 이 자료의 원문은 한국교육학술정보원에서 제공합니다. |
