Off-campus UMass Amherst users: To download campus access dissertations, please use the following link to log into our proxy server with your UMass Amherst user name and password.

Non-UMass Amherst users: Please talk to your librarian about requesting this dissertation through interlibrary loan.

Dissertations that have an embargo placed on them will not be available to anyone until the embargo expires.

Document Type

Campus-Only Access for Five (5) Years

Embargo Period

1-28-2020

Degree Program

Animal Science

Degree Type

Master of Science (M.S.)

Year Degree Awarded

2020

Month Degree Awarded

February

Abstract

Protein phosphatases regulate a wide array of proteins through post-translational modification and are required for a plethora of intracellular events in eukaryotes. While some core components of the protein phosphatase complexes are well characterized, many subunits of these large complexes remain unstudied. Here we characterize a murine loss-of-function allele of the protein phosphatase 1 regulatory subunit 35 (Ppp1r35) gene. Homozygous embryos lacking Ppp1r35 initiate developmental delay beginning at E7.5 and have obvious morphological defects at slightly later stages. Mutant embryos do not initiate turning and fail to progress beyond the size and relative development of an E8.5 embryo. Consistent with recent in vitro studies linking PPP1R35 with the microcephaly protein Rotatin and a role in centrosome elongation, we find that the Ppp1r35 mutant embryos lack primary cilia. Histological and molecular analysis of Ppp1r35 mutants revealed that notochord development is irregular and discontinuous and that the floor plate of the neural tube is not specified, consistent with defects in primary cilia. Similar to other mutant embryos with defects in centriole function, Ppp1r35 mutants display increased cell death that is prevalent in the neural tube and an increased number of proliferative cells in prometaphase. We hypothesize that loss of Ppp1r35 function abrogates centriole homeostasis, resulting in both a failure to produce functional primary cilia and cell death and/or cell cycle delay that leads to embryonic lethality. Taken together, these results highlight the essential function of Ppp1r35 during early mammalian development and implicate this gene as a candidate for human microcephaly.

DOI

https://doi.org/10.7275/6yts-rr04

First Advisor

Jesse Mager

Second Advisor

Kimberly D. Tremblay

Third Advisor

Dominique Alfandari

Share

COinS