Nonsense mutations in the ASPM gene have been most frequently identified among familial microcephaly patients. Depletion of ASPM causes spindle pole unfocusing during mitosis in multiple cell types of Drosophila. However, it remains unknown whether human ASPM has a similar function. Here, using CRISPR-based gene knockout (KO) and RNA interference combined with chemical inhibitors and auxin-indu...

Mutations in the MCPH1 (Microcephalin) and ASPM (abnormal spindle-like microcephaly associated) genes cause primary microcephaly. Both are centrosomal associated proteins involved in mitosis. Microcephalin plays an important role in DNA damage response and ASPM is required for correct division of proliferative neuro-epithelial cells of the developing brain. Reduced MCPH1 mRNA expression and ASP...

The microtubule-associated protein ASPM (abnormal spindle-like microcephaly-associated) plays an important role in spindle organization and cell division in mitosis and meiosis in lower animals, but its function in mouse oocyte meiosis has not been investigated. In this study, we characterized the localization and expression dynamics of ASPM during mouse oocyte meiotic maturation and analyzed t...

The most common cause of primary autosomal recessive microcephaly (MCPH) appears to be mutations in the ASPM gene which is involved in the regulation of neurogenesis. The predicted gene product contains two putative N-terminal calponin-homology (CH) domains and a block of putative calmodulin-binding IQ domains common in actin binding cytoskeletal and signaling proteins. Previous studies in mous...

with ASPM siRNA, there is defective cleavage furrow orientation, cytokinesis failure and an increase in apoptosis. Dominant negative expression of GFP-ASPM C-terminal fusion proteins induces cytokinesis failure in HeLa cells. To further investigate the functions of ASPM in cell division we are currently performing a foetal brain yeast two-hybrid (Y2H) screen to identify direct interactants of t...

Alterations in genes that regulate brain size may contribute to both microcephaly and brain tumor formation. Here, we report that Aspm, a gene that is mutated in familial microcephaly, regulates postnatal neurogenesis in the cerebellum and supports the growth of medulloblastoma, the most common malignant pediatric brain tumor. Cerebellar granule neuron progenitors (CGNPs) express Aspm when main...

The ASPM (abnormal spindle-like microcephaly-associated) protein has previously been implicated in the determination of human cerebral cortical size, but the cell biological basis of this regulation has not been studied. Here we investigate the role of Aspm in mouse embryonic neuroepithelial (NE) cells, the primary stem and progenitor cells of the mammalian brain. Aspm was found to be concentra...

We read with great interest the article by Vange et al [1] in the December 2015 issue of the Journal of Pathology, as well as the subsequent commentary by Zhu et al in the January 2016 issue [2]. Vange et al identified a novel possible oxyntic stem/progenitor cell marker ASPM [Asp (abnormal spindle) homologue, microcephaly-associated (Drosophila)] by genome-wide expression analysis of the micro...

with ASPM siRNA, there is defective cleavage furrow orientation, cytokinesis failure and an increase in apoptosis. Dominant negative expression of GFP-ASPM C-terminal fusion proteins induces cytokinesis failure in HeLa cells. To further investigate the functions of ASPM in cell division we are currently performing a foetal brain yeast two-hybrid (Y2H) screen to identify direct interactants of t...

Autosomal recessive primary microcephaly (MCPH) is a neural developmental disorder in which patients display significantly reduced brain size. Mutations in Abnormal Spindle Microcephaly (ASPM) are the most common cause of MCPH. Here, we investigate the underlying functions of Aspm in brain development and find that Aspm expression is critical for proper neurogenesis and neuronal migration. The ...