Cellular/Molecular
Neuroligin 1 and SynCAM: The Same and Different
Yildirim Sara, Thomas Biederer, Deniz Atasoy, Alexander Chubykin, Marina G. Mozhayeva, Thomas C. Südhof, and Ege T. Kavalali
(see pages 260-270)
Cell adhesion molecules are considered to be organizers at nascent synaptic contacts. But which ones, and how specific are such transsynaptic interactions? Neuroligin-1 (NL1) and SynCAM can induce “synapses” with neuronal axons when either molecule is expressed in “postsynaptic” non-neuronal cells. This week, Sara et al. show that the synaptogenic characteristics of these molecules are similar in artificial synapses but differ when expressed in neurons. They first cocultured hippocampal neurons with human embryonic kidney 293 (HEK293) cells transfected with NL1 or SynCAM. Presynaptic terminals were functional in neurons cocultured with cells expressing NL1 or SynCAM but not other adhesion molecules. Likewise, coexpression with glutamate receptors in HEK293 cells revealed spontaneous and evoked synaptic responses. However, when overexpressed in neurons, only NL1 increased the number of synapsin-labeled puncta, whereas only SynCAM enhanced the frequency of spontaneous miniature EPSCs at 7 d in vitro. Although the underlying mechanisms are not yet clear, the results point to distinct signaling mechanisms for these two synaptogenic molecules.
Development/Plasticity/Repair
A Sequence of Transcription Factors in Cortical Progenitor Cells
Chris Englund, Andy Fink, Charmaine Lau, Diane Pham, Ray A. M. Daza, Alessandro Bulfone, Tom Kowalczyk, and Robert F. Hevner
(see pages 247-251)
During development, differentiating neurons and glia express a variety of transcription factors that orchestrate this process. This week, Englund et al. examine transcription factors expressed by cells destined to become cortical pyramidal neurons. These neurons can arise directly from radial glial but also may pass through a transitional phase as intermediate progenitor cells (IPCs). Radial glial cells undergo mitosis at the ventricular surface, whereas IPCs divide within the ventricular zone (VZ) or subventricular zone (SVZ) and produce a strictly neuronal population. Using these geographical guidelines, the authors identified dividing cells in the VZ and SVZ that expressed IPC markers. IPCs were characterized by expression of Tbr2, a T-zone transcription factor, and by concurrent downregulation of Pax6, which is expressed by radial glia. Projection neurons expressed a different T-zone factor, Tbr1. Thus a Pax6→ Tbr2→ Tbr1 expression sequence marks cells as they pass from radial glia to IPC to neurons.
Expression of the transcription factors Pax6 (green), Tbr2 (red), and Tbr1 (blue) in embryonic day 14.5 mouse fore-brain (coronal section). Within the cortex, each transcription factor is expressed sequentially at different stages in the differentiation of cortical projection neurons. See the article by Englund et al. for details.
Behavioral/Systems/Cognitive
Squirrelvision: Orientation Tuning without Columns Stephen D. Van Hooser, J. Alexander F. Heimel, Sooyoung Chung, Sacha B. Nelson, and Louis J. Toth
(see pages 19-28)
In most mammals, including primates and tree shrews, the primary visual cortex is organized into columns in which the orientation preference of neurons remains constant. The preference changes smoothly along the topographical surface of the cortex, creating an orientation map. However, rodents and lagomorphs (i.e., rabbits) seemed to have paid no attention to this organizing principal. Van Hooser et al. hypothesized that the lack of a map in rodents might be attributable to reduced visual acuity or to a visual system too simple or too small. Using the gray squirrel, they found that none of these possibilities applied. Try as they might with imaging and single-unit recordings, the authors were unable to detect an orientation map or columnar organization. Nevertheless, single neurons definitely displayed orientation preference and a retinotopic map. It seems that a columnar organization of functional response properties is not a universal feature of the primary visual cortex.
Neurobiology of Disease
APH-1a Helps γ-Secretase Stick Together
Guojun Ma, Tong Li, Donald L. Price, and Philip C. Wong
(see pages 192-198)
Intramembraneous cleavage of amyloid precursor protein (APP) involving the γ-secretase complex results in pathological accumulations of β-amyloid (Aβ) peptides in Alzheimer's disease. γ-Secretase is also important for proteolysis of other proteins, such as Notch. APH-1, a seven-membrane-spanning member of the complex, exists in four separate isoforms. This week, Ma et al. examine the role of the 1a isoforms in γ-secretase function. They first report that an Aph-1a null mouse was embryonic lethal by embryonic day 11 (E11). Morphologically, the phenotype resembled Notch1, nicastrin, or presenilin knock-outs, consistent with a critical role for APH-1 in embryonic Notch signaling. In primary and immortalized fibroblasts from E9.5 knock-out mice, levels of the γ-secretase complex, its components, and Aβ peptides decreased, whereas APP accumulated. Even the early nicastrin/APH-1a subcomplex was absent, indicating the importance of APH-1 in assembly of the complex. Although APH-1a was critical during embryogenesis, expression of any of the isoforms rescued γ-secretase activity in vitro.
