The fine tuning of proliferation and neurogenesis, neuronal migration and differentiation and connectivity underlies the proper development of the cerebral cortex. Mutations in genes involved in these processes are responsible for neurodevelopmental disorders, such as cortical dysgeneses, which are usually associated with severe mental retardation and epilepsy. Over the past few years, the importance of cytoskeleton components in cellular processes crucial for cortical development has emerged from a body of functional data. This was reinforced by the association of mutations in the LIS1 and DCX genes, which both encode proteins involved in microtubule (MT) homeostasis, with cerebral cortex developmental disorders. The recent discovery of patients with lissencephaly and bilateral asymmetrical polymicrogyria (PMG) carrying mutations in the alpha- and beta-tubulin-encoding genes TUBA1A and TUBB2B further supports this view, and also raises interesting questions about the specific roles played by certain tubulin isotypes during the development of the cortex.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.tig.2009.10.003 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Centrosomal microtubule nucleation regulates radial migration of projection neurons independently of polarization in the developing brain.
Neuron
April 2023
Laboratory of Axonal Growth and Regeneration, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany. Electronic address:
Cortical projection neurons polarize and form an axon while migrating radially. Even though these dynamic processes are closely interwoven, they are regulated separately-the neurons terminate their migration when reaching their destination, the cortical plate, but continue to grow their axons. Here, we show that in rodents, the centrosome distinguishes these processes.
View Article and Find Full Text PDFOlfactory Development, Part 2: Neuroanatomic Maturation and Dysgeneses.
J Child Neurol
May 2017
1 Department of Paediatrics, University of Calgary and Alberta Children's Hospital Research Institute, Calgary, Alberta, Canada.
Olfactory axons project from nasal epithelium to the primitive telencephalon before olfactory bulbs form. Olfactory bulb neurons do not differentiate in situ but arrive via the rostral migratory stream. Synaptic glomeruli and concentric laminar architecture are unlike other cortices.
View Article and Find Full Text PDFTUBA1A mutation can cause a hydranencephaly-like severe form of cortical dysgenesis.
Sci Rep
October 2015
Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
TUBA1A mutations cause a wide spectrum of lissencephaly and brain malformations. Here, we report two patients with severe cortical dysgeneses, one with an extremely thin cerebral parenchyma apparently looking like hydranencephaly and the other with lissencephaly accompanied by marked hydrocephalus, both harbouring novel de novo missense mutations of TUBA1A. To elucidate how the various TUBA1A mutations affect the severity of the phenotype, we examined the capacity of the mutant protein to incorporate into the endogenous microtubule network in transfected COS7 cells by measuring line density using line extraction in an immunofluorescence study.
View Article and Find Full Text PDFTiming in neural maturation: arrest, delay, precociousness, and temporal determination of malformations.
Pediatr Neurol
May 2015
Department of Paediatrics, University of Calgary Faculty of Medicine and Alberta Children's Hospital Research Institute, Calgary, Alberta, Canada; Department of Radiology and Diagnostic Imaging, University of Calgary Faculty of Medicine and Alberta Children's Hospital Research Institute, Calgary, Alberta, Canada.
Timing is primordial in initiating and synchronizing each developmental process in tissue morphogenesis. Maturational arrest, delay, and precociousness all are conducive to neurological dysfunction and may determine different malformations depending on when in development the faulty timing occurred, regardless of the identification of a specific genetic mutation or an epigenetic teratogenic event. Delay and arrest are distinguished by whether further progressive development over time can be expected or the condition is static.
View Article and Find Full Text PDFNeuropathology of pediatric epilepsy.
Handb Clin Neurol
April 2014
Departments of Clinical Neurosciences and Paediatrics, Division of Paediatric Neurology, University of Calgary, Alberta Children's Hospital, Calgary, Canada. Electronic address:
The preoperative study of patients who are candidates for epilepsy surgery often classifies their epileptic foci as "lesional" or "non-lesional" based upon evidence from neuroimaging. Many lesions not detected by MRI are found by microscopic examination of the resected tissue. Advances have been made in neuropathological techniques to study resected brain tissue and to specify the types of focal cortical dysgeneses and other lesions by extending microscopic findings by applying immunocytochemical markers that identify specific types and distributions of neurons and glial cells that denote tissue architecture.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!