A novel role for 14-3-3ζ in coordinating interneuron development through regulation of Rac1 and non-canonical Shh signalling /

Date

2017

Authors

Greenberg, Zarina Isis,

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thesis

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Abstract

Schizophrenia is a devastating neurodevelopmental disorder widely believed to arise from defects during brain development. Indeed, dysfunction in the formation and function of GABAergic cortical interneurons has been implicated as a central pathogenic mechanism in this, and other, neurodevelopmental disorders. 14-3-3ζ is part of a family of highly conserved intracellular proteins, that bind to the phosphoserine/theronine sites on target proteins and is highly expressed in the brain. Interestingly, several findings in recent years implicate 14-3-3ζ as a candidate risk factor for schizophrenia including: 1) 14-3-3ζ is downregulated in post-mortem schizophrenic brain samples at the mRNA level; 2) 14-3-3ζ is downregulated across multiple neuroproteomic studies on schizophrenia patient samples; 3) linkage studies have implicated 14-3-3 family proteins in numerous neurodevelopmental disorders, and 4) genetic mutations in the gene encoding 14-3-3ζ (YWHAZ) have been found in schizophrenia patients. Previous studies have shown that 14-3-3ζ KO mice exhibit anatomical and behavioural traits akin to those seen in schizophrenia and other neurodevelopmental disorders.

School/Discipline

University of South Australia. School of Pharmacy and Medical Sciences.
School of Pharmacy and Medical Sciences.

Dissertation Note

Thesis (PhD(Medical Science))--University of South Australia, 2017.

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Copyright 2017 Zarina Isis Greenberg.

Description

1 ethesis (xviii, 196 pages) :
illustrations (some colour), charts (some colour)
Includes bibliographical references (pages 159-184)

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506 0#$fstar $2Unrestricted online access

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