Comparing placental phenotype similarities between Neuropathy Target Esterase and the Canonical Wnt Signaling Pathway

Abstract

A mass spectrometry analysis of Wnt components revealed that LGR with high probability to a protein called Neuropathy Target Esterase (NTE). This was interesting as both NTE and certain Wnt components were known to have placental phenotypes in mice. Therefore, the hypothesis arose that NTE could have a similar role or a potential interaction with the Wnt pathway. This thesis explores this possibility by first giving a detailed review of what is known to date about the Wnt signaling pathway and the NTE enzyme. This is followed by a description of normal placental development in mice and then a section on how this development is defective in both NTE knockout mice and mice with certain Wnt component mutations. Subsequently, an analysis comparing the phenotypes presented will be conducted and from this a discussion will be started. Following this extended literature review a scientific report will explore the protein R-Spondin and its function as an agonist for the canonical Wnt pathway as well as showing to which receptor it needs to bind for this role. This scientific report therefore underlines an important regulation component of the canonical Wnt pathway which is shown to play an important role in placental development. This thesis will conclude with a reflection describing the struggles and triumphs of the writing process as well as my time at Hubrecht Institute within the group of Dr. Hans Clevers under the guidance of Dr. Wim de Lau.