Poster abstracts
Poster number 81 submitted by Ramon Macias Jr
The Role of Tubb2a and Tubb2b in Embryonic Development
Ramon Macias (Molecular, Cellular, and Developmental Biology Graduate Program), Rolf W. Stottmann (Pediatrics, Ohio State University and Nationwide Childrens Hospital)
Abstract:
Microtubules are fundamental elements of the cytoskeleton. These are long arrays of alternating alpha and beta subunits. Humans have 9 beta and alpha tubulin genes, but little is known about the individual requirements of each gene throughout embryogenesis. During embryonic development, microtubules play a significant part in the proper formation of the brain, especially in the function of mitosis, intracellular transport, neuron morphology, cilia structure and flagellar motility. Defects in tubulin can disrupt these precise processes leading to structural brain abnormalities. TUBB2A and TUBB2B are two beta tubulin genes, that when mutated, have been linked to variety of congenital cortical malformations in human patients. The Tubb2a/b genes are 99.6 percent identical and very close together in the human and mouse genome. In general, tubulin genes are difficult to research due to the high sequence and structural homology between individual tubulin genes, making it quite difficult to create antibodies or RNA probes to precisely track specific tubulin proteins and/or transcripts. We have generated novel transgenic mice with epitope tags knocked into the endogenous locus of the Tubb2a and Tubb2b genes, allowing for precise tracking and therefore a clearer map of individual beta tubulin gene expression throughout development. Previous work has shown that individual deletion of either Tubb2a or Tubb2b has no major developmental phenotype – implying that other beta tubulins can compensate for the loss. To address the hypothesis that these genes act redundantly we have made a conditional allele of Tubb2a to pair with the Tubb2b deletion allele. We will present results of ongoing experiments removing both Tubb2a and Tubb2b from the entire embryo as well as just the developing forebrain.
Keywords: Beta Tubulin, Brain Development, Cilia