PubMed · 8752268
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
T J Sejnowski. 1996-08-29. Synapses get smarter.. https://doi.org/10.1038/382759a0
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
DNA packaging into heterochromatin is a fundamental mechanism of transcriptional silencing, yet its role in regulating neural progenitor behavior during brain development remains poorly understood. Trimethylation of histone H3 lysine 9 (H3K9me3), catalyzed by the methyltransferases SETDB1, SUV39H1, and SUV39H2, is a defining feature of heterochromatin, but functional redundancy among these enzymes has obscured their developmental roles. Here, we generated a cortex-specific triple knockout mouse model lacking Setdb1, Suv39h1, and Suv39h2 to directly interrogate H3K9me3 function during corticogenesis. Combined loss of H3K9 methyltransferases caused genome-wide depletion of H3K9me3, disruption of neural progenitor cell-cycle progression, and impaired cortical neurogenesis, resulting in microcephaly. H3K9 methyltransferases preserve neural progenitor identity and function by silencing clustered protocadherins, meiosis-associated genes, and a cell-cycle restraint program through H3K9me3 deposition. Loss of H3K9me3 promoted local chromatin opening and increased transcription factor occupancy, enabling transposable elements to acquire cryptic enhancer activity and modulate proximal gene expression. Together, these findings establish H3K9me3 heterochromatin as an active regulator of neural progenitor dynamics and lineage fidelity, revealing a central epigenetic mechanism that restricts aberrant transcriptional programs to ensure cortical growth.
Polymicrogyria (PMG) is one of a large group of human cortical malformations that collectively account for a significant percentage of patients with epilepsy, congenital neurological deficits, and intellectual disability. PMG is characterized by an excess of small gyri and abnormal cortical lamination. The most common distribution is bilateral, symmetrical, and maximal, in the region surrounding the sylvian fissures, and is known as "bilateral perisylvian polymicrogyria" (BPP). Most cases are sporadic, although several families have been observed with multiple affected members, usually following an X-linked inheritance pattern. Here we report the first genetic locus for BPP mapped by linkage analysis in five families. Linkage places the critical region for BPP at Xq28 (LOD score 3.08 in Xq28, distal to DXS8103 by multipoint analysis). We suggest that this region contains a gene that is necessary for correct neuronal organization and that the identification of this gene will both enhance our understanding of normal cortical development and accelerate the identification of other genes responsible for PMG.
With the advent of event-related paradigms in functional MRI, there has been interest in finding the optimal stimulus timing, especially when the interstimulus interval is varied during the imaging run. Previous works have proposed stimulus timings to optimize either the estimation of the impulse response function (IRF) or the detection of signal changes. The purpose of this paper is to clarify that estimation and detection are fundamentally different goals and to determine the optimal stimulus timing and distribution with respect to both the accuracy of estimating the IRF and the power of detection assuming a particular hemodynamic model. Simulated stimulus distributions are varied systematically, from traditional blocked designs to rapidly varying event related designs. These simulations indicate that estimation of the hemodynamic impulse response function is optimized when stimuli are frequently alternated between task and control states, with shorter interstimulus intervals and stimulus durations, whereas the detection of activated areas is optimized by blocked designs. The stimulus timing for a given experiment should therefore be generated with the required detectability and estimation accuracy.