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A Citrullination-Deficient Zebrafish Model Reveals a Role for Padi2 in Fin Regeneration
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| 자료유형 | 학위논문 |
|---|---|
| 서명/저자사항 | A Citrullination-Deficient Zebrafish Model Reveals a Role for Padi2 in Fin Regeneration. |
| 개인저자 | Golenberg, Netta. |
| 단체저자명 | The University of Wisconsin - Madison. Cellular & Molecular Bio - AG. |
| 발행사항 | [S.l.]: The University of Wisconsin - Madison., 2019. |
| 발행사항 | Ann Arbor: ProQuest Dissertations & Theses, 2019. |
| 형태사항 | 137 p. |
| 기본자료 저록 | Dissertations Abstracts International 81-03B. Dissertation Abstract International |
| ISBN | 9781085653268 |
| 학위논문주기 | Thesis (Ph.D.)--The University of Wisconsin - Madison, 2019. |
| 일반주기 |
Source: Dissertations Abstracts International, Volume: 81-03, Section: B.
Advisor: Huttenlocher, Anna. |
| 이용제한사항 | This item must not be sold to any third party vendors. |
| 요약 | The study of regenerative medicine is essential to identify both common cellular pathways activated during efficient regeneration and the detrimental responses that are responsible for poor regeneration in human wound healing. Mammals have limited regenerative capacity with wound healing resulting in the maintenance of structural integrity, but the loss of organ/tissue function. Mammalian wounds have persistent leukocyte recruitment and the deposition of a fibrin-rich scar. Conversely, a hallmark of efficient regeneration in multiple regenerative model organisms is the presence of a mesenchymal-cell signaling center called the blastema which is responsible for promoting cell proliferation. In simpler vertebrate models of regeneration, early signals have been identified that are required for late-stage regeneration including early calcium signaling. However, the mechanism by which early calcium flux promotes late regeneration is unknown. This dissertation focuses on the function of the calcium-dependent enzyme, Peptidylarginine deiminase-2 (Padi2) and its enzymatic activity, citrullination. PADI enzymes are known to play a pathogenic role in autoimmune disorders and have recently been associated with pluripotency in stem cells. We first sought to develop a loss-of-function mutant for zebrafish Padi2 and demonstrated that although Padi2 mutant zebrafish lack citrullination, the mutants are viable and fertile. Examination of cellular development revealed that padi2-mutant larvae have increased neuromuscular junctions. We characterized the role of citrullination during regeneration and discovered a localized group of cells with citrullinated histones activated upon wounding. Loss of Padi2 in our mutant resulted in the absence of wound-induced citrullination of histones and impaired fin regeneration after tail transection. During regeneration, Padi2-mutants had increased and persistent neutrophil recruitment to the wound and decreased wound proliferation when compared to wildtype larvae. We have demonstrated a positive role of citrullination in regeneration, potentially through the promotion of a stem-cell like state within the premature blastema. Together, our results demonstrate that citrullination plays a role in neuromuscular development and in the regenerative wound response. These findings identify a new role for citrullination in wound healing and has implications to citrullination-related diseases including autoimmune disorders and cancers. |
| 일반주제명 | Molecular biology. Biology. Developmental biology. |
| 언어 | 영어 |
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