Developmental perturbation in early embryogenesis persist to impair neuronal function in adults
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Abstract
Animal body plans tend to display external symmetry; however, their internal organs can be anatomically and/or functionally asymmetrical. Visceral organs such as liver, heart, and pancreas show clear anatomical asymmetry in a bilateral fashion. The right and left cerebral hemispheres are functionally asymmetric and small deviations have been correlated with pathologies such as schizophrenia and bipolar disorders. The bilateral asymmetry is genetically and developmentally defined as a third axis as are the other two axes: anterior/posterior and dorsal/ventral. The lab model Caenorhabditis elegans is particularly suited to study left/right (L/R) asymmetry. Like most other animals, C. elegans shows predominantly bilaterally symmetric external anatomy, but clear bilateral asymmetry in the viscera, a key feature being the placement of the anterior gonad towards the right. In addition to anatomical asymmetry certain neuronal pairs such as AWC-L and AWC-R also display functional asymmetry. The anatomic bilateral asymmetry is discernible during the initial cell divisions of the fertilized egg. Previous studies have suggested that PAR proteins along with Gα proteins associated with spindle positioning that play a role in anterior/posterior and dorsal-ventral are are likely to underlie the first symmetry–breaking step as well. The absence of gpa-16, a Gα protein, has been shown to yield up to 50% sinistral worms. On the contrary, wild type N2 animals invariably lead to dextral embryos. We have investigated the direct effects of disrupted asymmetry on embryonic lethality and adult behavior. Here, we show that the absence of gpa-16 results in not only sinistral embryos but also randomly dividing embryos. Surviving adults with the gpa-16 mutation are impaired in both, associative and non-associative learning. We are examining if the reversed asymmetry manifests its functional effects on behavior due to potentially atypical neuronal circuitry and looking at synaptic connectivity of gpa-16 mutants with the goal of unraveling anatomically atypical circuits.