Human birth defects and cancers are often caused by misregulation of the Wnt signaling pathway. In early vertebrate embryos, development of the body axis critically requires the activation of the Wnt pathway on one side of the embryo. In the frog Xenopus, a predominant model organism for axis formation, asymmetric Wnt signaling is achieved by the differential localization of maternally derived molecules stored in the egg. These determinants are translocated toward the future dorsal side by microtubule-based rotational movements of the egg cortex following fertilization. Interference with this process results in embryos lacking the dorsal tissues. The exact mechanisms regulating asymmetry in cortical rotation and Wnt activation in axis formation remain unclear. Data from maternal loss-of- function studies, including preliminary studies for this proposal, have implicated vegetally localized factors. The long-term goal of this research is to understand the role of these localized maternal gene products in embryonic axis formation. Preliminary studies for this proposal have identified a potential for maternal Wnt signals in regulating cortical rotation. Novel methods for monitoring microtubule dynamics during cortical rotation in vivo are also employed. The objectives of this proposal are to determine mechanisms underlying the formation of the vegetal microtubule array and to characterize potential determinants carried on the array.
The specific aims are to determine the roles of localized mRNAs in controlling microtubule assembly during the cortical rotation, to determine the extent this process is regulated by ongoing Wnt signaling in the oocyte and to characterize protein determinants in the vegetal cortex.
The findings of these proposed studies are relevant to, and will benefit public health by enhancing the understanding of basic signaling pathways involved in cell and tissue differentiation which are conserved in human development. Novel insights will be gained into these mechanisms and will be an essential step toward improving the diagnosis, prevention and treatment of human birth defects and genetic diseases.
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|Elliott, Karen L; Houston, Douglas W; DeCook, Rhonda et al. (2015) Ear manipulations reveal a critical period for survival and dendritic development at the single-cell level in Mauthner neurons. Dev Neurobiol 75:1339-51|
|Elliott, Karen L; Houston, Douglas W; Fritzsch, Bernd (2015) Sensory afferent segregation in three-eared frogs resemble the dominance columns observed in three-eyed frogs. Sci Rep 5:8338|
|Olson, David J; Oh, Denise; Houston, Douglas W (2015) The dynamics of plus end polarization and microtubule assembly during Xenopus cortical rotation. Dev Biol 401:249-63|
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|Hulstrand, Alissa M; Houston, Douglas W (2013) Regulation of neurogenesis by Fgf8a requires Cdc42 signaling and a novel Cdc42 effector protein. Dev Biol 382:385-99|
|Bassuk, Alexander G; Muthuswamy, Lakshmi B; Boland, Riley et al. (2013) Copy number variation analysis implicates the cell polarity gene glypican 5 as a human spina bifida candidate gene. Hum Mol Genet 22:1097-111|
|Elliott, Karen L; Houston, Douglas W; Fritzsch, Bernd (2013) Transplantation of Xenopus laevis tissues to determine the ability of motor neurons to acquire a novel target. PLoS One 8:e55541|
|Mei, Wenyan; Jin, Zhigang; Lai, Fangfang et al. (2013) Maternal Dead-End1 is required for vegetal cortical microtubule assembly during Xenopus axis specification. Development 140:2334-44|
|Schneider, Patricia N; Slusarski, Diane C; Houston, Douglas W (2012) Differential role of Axin RGS domain function in Wnt signaling during anteroposterior patterning and maternal axis formation. PLoS One 7:e44096|
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