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From signal to shape: investigating how signaling pathways generate a newly evolved morphology

Smith, Sarah (2020) From signal to shape: investigating how signaling pathways generate a newly evolved morphology. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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The development of anatomical form is multifaceted, involving both the patterning of gene expression and the morphogenesis of tissues at the cellular level. However, our understanding of how these two processes are integrated remains unclear. Studies of rapidly evolving anatomical structures address this question by identifying genetic alterations that affect morphogenesis. I examined the posterior lobe, a recently evolved appendage-like structure on the genitalia of members of the Drosophila melanogaster clade. During posterior lobe development, expansion of unpaired (upd), a ligand of the JAK/STAT pathway, is observed in species that develop this structure. I characterized the regulatory region of upd and uncovered a posterior lobe enhancer. Through CRISPR/Cas9 deletion of this enhancer, I found that it is vital for expression of upd in the posterior lobe and is required for proper lobe development. To investigate how expansion of JAK/STAT signaling contributed to posterior lobe development, I measured its cellular morphology and found that the posterior lobe forms through elongation of cells along their apico-basal axis. I identified the differential expression and deposition of the apical extracellular matrix (aECM) protein Dumpy and demonstrated a requirement for dumpy during posterior lobe development and evolution. In addition, I have identified a required role for the cellular effector, short stop (shot), which may act cooperatively with or in in parallel to Dumpy. I have determined that shot is regulated by the JAK/STAT pathway in the cells of the posterior lobe. This work highlights the complexity of development by linking the expanded expression of a signaling pathway ligand with a novel morphogenetic process through the activation of a cellular effector. In addition this research uncovered a yet unseen role for the aECM in evolution of novel morphologies, emphasizing its novel role in regulating extreme changes in cell height.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Smith, Sarahsjs152@pitt.edusjs152
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee MemberCampbell, Gerardcamp@pitt.educamp
Committee ChairRebeiz, Markrebeiz@pitt.edurebeiz
Committee MemberHildebrand, Jeffreyjeffh@pitt.edujeffh
Committee MemberChapman, Deborahdlc7@pitt.edudlc7
Committee MemberDavidson, Lancelad43@pitt.edulad43
Date: 16 January 2020
Date Type: Publication
Defense Date: 8 August 2019
Approval Date: 16 January 2020
Submission Date: 29 October 2019
Access Restriction: 2 year -- Restrict access to University of Pittsburgh for a period of 2 years.
Number of Pages: 173
Institution: University of Pittsburgh
Schools and Programs: Dietrich School of Arts and Sciences > Biological Sciences
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: evolution; development; drosophila; morphogenesis, extracellular matrix
Date Deposited: 16 Jan 2020 19:45
Last Modified: 16 Jan 2022 06:15


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