843B Poster - 13. Neural development and physiology
Friday April 08, 2:00 PM - 4:00 PM

Authors:
Shalini Chakraborty; Todd Schoborg

Affiliation: University of Wyoming

Keywords:
m. CNS; a. cytoskeleton

Autosomal recessive primary microcephaly (MCPH) is a congenital condition which is characterized by smaller brain size, intellectual disabilities, and life span reduction. Human MCPH is most commonly caused by homozygous mutations in the abnormal spindle like microcephaly associated (aspm) gene, which has a Drosophila ortholog called abnormal spindle (asp). Recent structure-function studies from our lab have identified a ͠ 600 amino acid ‘minimal fragment’ (Asp^MF) of Asp’s N-terminus that is sufficient to rescue brain size in asp mutant flies. Although the MCPH phenotype is clinically well-characterized, the cellular basis of this disorder remains unknown. As an approach to uncover the cellular and molecular basis of MCPH, we employed a high-definition yeast two hybrid (Y2H) screen to identify potential interactors of Asp^MF. Using a third-instar larval brain cDNA library, we screened over 100 million potential domain-level interactions with Asp^MF. Gene ontology analysis of the candidate interactors revealed molecular functions including microtubule and actin cytoskeleton related functions in addition to signaling pathways involved in cell differentiation. Genetic rescue experiments suggest that these interactions are specifically required in neuroepithelial and lamina precursor cells of the larval brain during the neurogenic time window of development in order to promote proper brain size and morphology. We will discuss these ongoing studies to identify the molecular basis of MCPH and Asp’s ability to promote proper brain growth and development