The Role of Gm572 in Left-Right Patterning

Date of Award

Spring 2022

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Genetics

First Advisor

Liem, Karel

Abstract

Breakage of left-right symmetry is an evolutionarily conserved process in the establishment of the vertebrate body plan. In the mouse, this process is initiated at the left-right organizer and requires cilia. While some details of the steps in left-right patterning have been previously determined, the exact mechanisms for certain steps remain unclear. Therefore, the identification of new genes involved in left-right patterning would enhance the current understanding of the different steps that are involved. Here, a forward genetic screen was performed to identify new genes involved in vertebrate embryonic development. Subsequently, we identified the mouse mutant doppelgänger (dopp) that showed defects in left-right patterning as a result of a point mutation in the novel gene Gm572. We show that GM572 is a secreted glycosylated protein that is expressed at the left-right organizer in E7.5 mouse embryos. We also show that GM572 interacts with proteins that are required to transduce a flow-mediated signal to initiate the nodal cascade. Overall, we show that Gm572 is a novel gene that is required for the specification of the left side during mouse embryonic development.

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