Date of Degree
PhD (Doctor of Philosophy)
Houston, Douglas W
First Committee Member
Cornell, Robert A
Second Committee Member
Slusarski, Diane C
Third Committee Member
Weeks, Daniel L
Fourth Committee Member
Weiner, Joshua A
The vegetal cortex of the Xenopus oocyte is enriched for several mRNAs critical for early embryonic developmental processes, including germ layer specification and dorsoventral axis formation. A recent microarray screen for other vegetally localized RNAs identified several hundred novel cortex-enriched transcripts, which may have undiscovered roles in early development. In order to better elucidate the functions of localized mRNAs in early development, I characterized the spatiotemporal expression patterns and developmental functions of two novel transcripts, TRIO and F-actin binding protein (triobp) and Cdc42 effector protein 4-like (cep4l).
Overexpression and loss-of-function experiments failed to identify a critical role for TrioBP in early Xenopus development. For Cep4l, I found that overexpression of Cep4l induced primary neuron formation throughout the epidermis, preferentially inducing primary sensory neurons. This increase came at the expense of neighboring non-neuronal ciliated and ion-secreting cells, suggesting a role for Cep4l in neural boundary formation. Additionally, I have shown that Cep4l binds specifically to Cdc42 through its known Cdc42/Rac-interactive binding (CRIB) domain, and that this activation was necessary for Cep4l function.
Morpholino (MO) oligonucleotide based inhibition of Cep4l protein synthesis resulted in decreased primary sensory neurogenesis. Additionally, I have shown that Cdc42 itself is required for sensory neurogenesis. Furthermore, I find that Fgf8a, an isoform of Fgf8 previously known to regulate neuronal development, but not the Fgf8b isoform, regulates the association of Cep4l and Cdc42. Importantly, I further show that Cep4l and Cdc42 are required for the ability of Fgf8a to induce sensory neurons.
Overall, this work suggests a novel role for Cep4l and Cdc42 in the regulation of primary sensory neuronal fate downstream of a unique Fgf8 signaling pathway. I propose that binding of Fgf8a to its receptors activates Cdc42 and recruits Cep4l, which could serve as a scaffold for integrating additional signaling pathways involved in controlling sensory neuron fate.
Cdc42, Fgf8a, neurogenesis, Xenopus
ix, 123 pages
Includes bibliographical references (pages 115-123).
Copyright 2013 Alissa Marie Hulstrand
Hulstrand, Alissa Marie. "Characterization of a Cdc42 effector protein (Cep4l) and a novel role for Cdc42 in xenopus neurogenesis and Fgf signaling." PhD (Doctor of Philosophy) thesis, University of Iowa, 2013.