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The Journal of Neuroscience, June 23, 2004, 24(25)
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This Week in The Journal
Cellular/Molecular
Collybistin and Gephyrin in Receptor Clustering
Kirsten Harvey, Ian C. Duguid, Melissa J. Alldred, Sarah E. Beatty, Hamish Ward, Nicholas H. Keep, Sue E. Lingenfelter, Brian R. Pearce, Johan Lundgren, Michael J. Owen, Trevor G. Smart, Bernhard Lüscher, Mark I. Rees, and Robert J. Harvey
(see pages 5816-5826)
Inhibitory GABAergic and glycinergic transmission depend on receptor clustering at postsynaptic sites juxtaposed to pre-synaptic release sites. This spatial segregation relies on an associated protein, gephyrin, which itself is directed to the membrane by the recently characterized GDP-GTP exchange factor collybistin. In this issue, Harvey et al. characterize several variants of collybistin generated by splicing within the N-terminal src homology 3 (SH3) domain as well as the C-terminus domain. The SH3 domain diminishes the ability of collybistin to facilitate submembrane aggregates of gephyrin. The authors also report that collybistin and the glycine
subunit bind to the C-terminal domain in gephyrin. They identified a mutation in the human collybistin gene ARHGEF9 that causes hyperekplexia, a heritable disease that results in an excessive startle response. This disorder has been associated previously with mutations in either glycine receptor
or
Development/Plasticity/Repair
Roofing the Chick Spinal Cord
Victor V. Chizhikov and Kathleen J. Millen
(see pages 5694-5702)
The roof plate is a developmentally intermediate structure of non-neuronal cells that guides differentiation, specification, and connectivity of dorsal interneurons. This week, Chizhikov and Millen explore the actions of the homeobox domain transcription factor Lmx1b in directing formation of the dorsal spinal cord. They used in ovo electroporation to manipulate expression of signaling molecules and determine their contributions to spinal cord development. In chick embryos, in which both Lmx1a and Lmx1b are expressed, Lmx1b acted upstream of Lmx1a to direct roof-plate formation. Patterning in the dorsal spinal cord was subsequently directed by the signaling molecules Bmp and, to a lesser extent, Wnt. Embryonic mice do not express Lmx1b in the roof plate, so signaling there relies entirely on Lmx1a. However in dreher mice, which lack Lmx1a, transfection with Lmx1b partially rescued roof-plate signaling and formation, indicating some functional redundancy in these related transcription factors.
Behavioral/Systems/Cognitive
En1 Interneurons in Frogs and Fish
Shin-ichi Higashijima, Mark A. Masino, Gail Mandel, and Joseph R. Fetcho
(see pages 5827-5839)
W.-C. Li, Shin-ichi Higashijima, D. M. Parry, Alan Roberts, and S. R. Soffe
(see pages 5840-5848)
A pair of papers in this week's Journal probes the origin of a primitive class of inhibitory spinal interneurons that expresses the Engrailed-1 (En1) transcription factor. Li et al. examined Xenopus tadpoles; Higashijima et al. examined zebrafish larvae. In these preparations, En1 is restricted to a morphologically similar group of spinal interneurons. Using genetic and electrophysiological techniques, the groups describe that these ascending interneurons mediate glycinergic inhibition of both incoming sensory activity in the dorsal spinal cord as well as motoneurons and descending interneurons in the ventral cord. As a result, these cells modulate motor pattern generation as well as sensory gating functions. In fact, this distinct class of interneurons provides all of the ipsilateral inhibition in the developing Xenopus and zebrafish spinal cord, thus allowing reflex responses to touch to be coordinated with ongoing swimming.
Neurobiology of Disease
Stroke and Neurogenesis in the SVZ
Ruilan Zhang, Zhenggang Zhang, Chunling Zhang, Li Zhang, Adam Robin, Ying Wang, Mei Lu, and Michael Chopp
(see pages 5810-5815)
Stroke increases neurogenesis in the subventricular zone (SVZ), the site of neuronal progenitor cells in the adult brain. The orientation of cell cleavage in dividing cells can be vertical, resulting in symmetrical divisions, or horizontal, producing asymmetrical divisions. Symmetrical divisions produce two identical progenitor cells that remain in the ventricular zone, whereas asymmetrical divisions produce one progenitor and one postmitotic neuron. The postmitotic neuron then migrates to the olfactory bulb. The former mechanism replenishes the progenitor pool, and the latter increases neuronal production. Zhang et al. traced the origins of new neurons that emerge after ischemia caused by middle cerebral occlusion in the adult rat. Four days after the stroke, cell divisions increased twofold in the SVZ along with an increase in symmetrical divisions. Furthermore, the neuronal marker TuJ1 also increased, consistent with an increase in neuronal differentiation. The authors conclude that the transient increase in symmetrical divisions expands the pool of progenitors, and thus may support subsequent enhanced neurogenesis.
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A-C show the cleavage orientations (vertical, horizontal, and oblique) of dividing cells in the SVZ with respect to the surface of the lateral ventricle (Lv). See the article by Zhang et al. for details.
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