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Elucidating the Role of Mechanics in Neural Plate Convergent Extension

Vijayraghavan, Deepthi (2018) Elucidating the Role of Mechanics in Neural Plate Convergent Extension. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Neural tube formation is crucial for the proper development of the brain and spinal cord and its failure results in congenital disorders known as neural tube defects (NTDs). Several known genetic mutations are associated with NTDs but the physical mechanisms by which they affect neural tube morphogenesis remain unclear. The neural tube begins as an epithelial sheet on the embryo surface called the neural plate that undergoes a series of shape changes to form an elongated tubular structure, internalized within the embryo. Integrated behaviors of embryonic cells orchestrate these tissue-level deformations. Our study aimed to identify the cell behaviors accompanying early neural plate shaping in Xenopus laevis embryos when the tissue elongates in the anterior-posterior axis while narrowing in a perpendicular mediolateral axis. Through observation and quantification of local cell and tissue mechanical strains, we identified the emergence of distinctive spatiotemporal patterns of cell behavior. Cells undergo oriented rearrangements within the medial neural plate whereas at its lateral edges, cells assume an elongated morphology.

Among the mutations associated with human NTDs, planar cell polarity (PCP) pathway mutations are known to inhibit plate narrowing and elongation and prevent cell rearrangements in vertebrate models of human development. As a cell’s local tissue mechanical environment can influence its behaviors, we sought to determine whether the lack of rearrangement in PCP-compromised embryos might be due to the lack of tissue deformation. We tested how wild type and PCP-compromised plate cells behave in altered tissue strain environments. We find that medial plate cell rearrangement is an intrinsic program independent of tissue extension; however, lateral cell elongation is likely strain dependent. PCP compromised cells in a narrowing and extending tissue assume an elongated morphology compared to wild type cells, becoming stretched in the direction of tissue elongation. These distinctive behaviors under similar mechanical conditions suggest that the PCP pathway mediates a cell's response to its mechanical microenvironment, guiding morphology during plate shaping. This dissertation exposes a role for tissue mechanics in the PCP-mutant phenotype and provides a framework to test the interplay between tissue mechanics and planar patterning in guiding cell behaviors during neural tube morphogenesis.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Vijayraghavan, Deepthideepthi.07@gmail.comdsv1
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairDavidson, Lance
Committee MemberBanerjee, Ipsita
Committee MemberHildebrand, Jeffrey
Committee MemberRoy, Partha
Date: 25 January 2018
Date Type: Publication
Defense Date: 15 September 2017
Approval Date: 25 January 2018
Submission Date: 17 November 2017
Access Restriction: 1 year -- Restrict access to University of Pittsburgh for a period of 1 year.
Number of Pages: 150
Institution: University of Pittsburgh
Schools and Programs: Swanson School of Engineering > Bioengineering
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: Neural Tube, Xenopus laevis, Morphogenesis, Epithelium, tissue strain, Developmental Biomechanics, Epithelial morphogenesis, Convergetn Extension
Date Deposited: 25 Jan 2018 13:07
Last Modified: 25 Jan 2019 06:15


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