This Week in The Journal

Cellular/Molecular

Nucleosome Remodeling Is Required for Myelination

Holly Hung, Rebecca Kohnken, and John Svaren

Within cell nuclei, DNA is condensed by wrapping sequential sections around clusters of histone proteins, forming a string of nucleosomes. How tightly DNA is wrapped and where on the strand nucleosomes are positioned are determined by nucleosome remodeling complexes. Covalent modification of histones also influences how tightly DNA is wound, which, in turn, determines whether other proteins can interact with DNA—for example, to initiate transcription. By such regulation, nucleosome remodeling complexes and histone-modifying proteins play central roles in differentiation. The nucleosome remodeling and deacetylase (NuRD) complex uniquely comprises both types of proteins. The histone deacetylase component has been shown to be required for myelination in the PNS, and Hung et al. demonstrate that the nucleosome remodeling component is also required. Knocking out this component in mouse Schwann cells impaired myelination, apparently by reducing repression of genes expressed in proliferating Schwann cells and reducing expression of genes required in mature myelin.

Development/Plasticity/Repair

Time and Lineage Specify Cell Fate in Ventral Spinal Cord

Chie Satou, Yukiko Kimura, and Shin-ichi Higashijima

(see pages 1771–1783)

Early in development, the neural tube is divided into subregions by gradients of morphogens along rostrocaudal and dorsoventral axes. Floor plate cells of the developing spinal cord secrete Sonic hedgehog (Shh), which induces differentiation of ventral progenitors. Varying concentrations of Shh along the dorsoventral axis induce expression and repression of different transcription factors, which divides the ventral cord into five domains that give rise to distinct neuronal classes. Some domains produce multiple classes of neurons, but how cell fate is restricted within domains is poorly understood. By tracing lineages in zebrafish, Satou et al. discovered that the dorsal-most domain of ventral precursors gives rise to five classes of inhibitory and excitatory commissural interneurons distinguishable by neurotransmitter type, position, and axonal projection pattern. The five types emerged from three distinct precursor types in a specific temporal order. These results lay the groundwork for determining how molecular signals specify cell fate within this domain.

Neurons in the developing zebrafish. Neurons of the dorsal-most domain in ventral spinal cord are yellow; other neurons are red. See the article by Satou et al. for details.

Behavioral/Systems/Cognitive

Neural Envelope Is Used to Decipher Speech in Noise

Jayaganesh Swaminathan and Michael G. Heinz

(see pages 1747–1756)

Complex waveforms can be described as the sum of sinusoids of different frequencies or, alternatively, as a combination of a rapidly varying temporal fine structure (TFS) and a slowly varying contour, or envelope. Cochlear hair cells separate sounds into their component frequencies, but the presence of TFS- and envelope-sensitive neurons in the auditory brainstem suggest these features are reconstructed centrally. Combining the TFS of one sound with the envelope of another has demonstrated that the envelope is important for deciphering speech, whereas TFS is used to discern pitch and location. Some studies have suggested, however, that speech in noisy environments relies on TFS. Swaminathan and Heinz note that because hair cells filter sounds, the reconstructed neural envelope likely differs from the original acoustic envelope. Using a computational model to predict the neural TFS and envelope, they conclude that people rely largely on the neural envelope to decipher speech even in noisy environments, but TFS boosts discrimination.

Neurobiology of Disease

PTEN Knock-out Increases Synaptic Responses

Qiaojie Xiong, Hysell V. Oviedo, Lloyd C. Trotman, and Anthony M. Zador

(see pages 1643–1652)

The phosphatase and tensin homolog PTEN antagonizes the activity of phosphoinositide 3-kinases, including the mammalian target of rapamycin (mTOR), which act downstream of growth factor receptors. Thus, PTEN prevents excessive growth, like that occurring in cancers; indeed, PTEN mutation is linked to tumorigenesis. But PTEN mutations are also linked to other neurological conditions, including autism spectrum disorders (ASDs). PTEN knock-out increases axonal and dendritic growth and spine density, but whether such changes contribute to ASDs is unclear. To examine possible effects on connectivity, Xiong et al. knocked out PTEN in a subset of auditory cortical neurons in young mice, then activated local or long-range inputs. In all cases, postsynaptic responses were larger in PTEN-null pyramidal neurons than in nearby PTEN-expressing neurons. The frequency and amplitude of miniature EPSCs also increased. These effects, and exuberant dendritic growth, were blocked by inhibiting mTOR complex 1. Whether such hyperconnectivity underlies ASDs remains to be determined.