Originally published as Genetics Published Articles Ahead of Print on June 18, 2008.

Genetics, Vol. 179, 1327-1336, July 2008, Copyright © 2008
doi:10.1534/genetics.108.088435

Pleiotropic Effects of Drosophila neuralized on Complex Behaviors and Brain Structure

Stephanie M. Rollmann^*,,1,2, Liesbeth Zwarts^,1, Alexis C. Edwards^,, Akihiko Yamamoto^*,, Patrick Callaerts, Koenraad Norga^,**, Trudy F. C. Mackay^, and Robert R. H. Anholt^*,,,3

^* Department of Zoology, North Carolina State University, Raleigh, North Carolina 27695-7617, W. M. Keck Center for Behavioral Biology, North Carolina State University, Raleigh, North Carolina 27695-7617, Laboratory of Developmental Genetics, VIB-PRJ8 and Katholieke Universiteit Leuven, Center for Human Genetics, B-3000 Leuven, Belgium, Department of Genetics, North Carolina State University, Raleigh, North Carolina 27695-7614 and ^** Children's Hospital, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium

³ Corresponding author: W. M. Keck Center for Behavioral Biology, Campus Box 7617, North Carolina State University, Raleigh, NC 27695-7617.
E-mail: anholt{at}ncsu.edu

Understanding how genotypic variation influences variation in brain structures and behavioral phenotypes represents a central challenge in behavioral genetics. In Drosophila melanogaster, the neuralized (neur) gene plays a key role in development of the nervous system. Different P-element insertional mutations of neur allow the development of viable and fertile adults with profoundly altered behavioral phenotypes that depend on the exact location of the inserted P element. The neur mutants exhibit reduced responsiveness to noxious olfactory and mechanosensory stimulation and increased aggression when limited food is presented after a period of food deprivation. These behavioral phenotypes are correlated with distinct structural changes in integrative centers in the brain, the mushroom bodies, and the ellipsoid body of the central complex. Transcriptional profiling of neur mutants revealed considerable overlap among ensembles of coregulated genes in the different mutants, but also distinct allele-specific differences. The diverse phenotypic effects arising from nearby P-element insertions in neur provide a new appreciation of the concept of allelic effects on phenotype, in which the wild type and null mutant are at the extreme ends of a continuum of pleiotropic allelic effects.

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