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.

Public Health Relevance

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.

National Institute of Health (NIH)
Research Project (R01)
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Development - 2 Study Section (DEV2)
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Hoodbhoy, Tanya
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University of Iowa
Schools of Arts and Sciences
Iowa City
United States
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Houston, Douglas W (2013) Regulation of cell polarity and RNA localization in vertebrate oocytes. Int Rev Cell Mol Biol 306:127-85
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
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
Schneider, Patricia N; Olthoff, John T; Matthews, Abby J et al. (2011) Use of fully modified 2'-O-methyl antisense oligos for loss-of-function studies in vertebrate embryos. Genesis 49:117-23
Hulstrand, Alissa M; Schneider, Patricia N; Houston, Douglas W (2010) The use of antisense oligonucleotides in Xenopus oocytes. Methods 51:75-81
Schneider, Patricia N; Hulstrand, Alissa M; Houston, Douglas W (2010) Fertilization of Xenopus oocytes using the host transfer method. J Vis Exp :
Cuykendall, Tawny N; Houston, Douglas W (2010) Identification of germ plasm-associated transcripts by microarray analysis of Xenopus vegetal cortex RNA. Dev Dyn 239:1838-48
Cuykendall, Tawny N; Houston, Douglas W (2009) Vegetally localized Xenopus trim36 regulates cortical rotation and dorsal axis formation. Development 136:3057-65