1. Zooming in on Touch Transduction in C. elegans
Juan G. Cueva, Atticus Mulholland, and Miriam B. Goodman
Cueva et al. wanted to see just how mechano-electrical transduction (MeT) channels open in Caenorhabditis elegans. The prevailing idea is that 15-protofilament microtubules and an electrondense extracellular matrix serve as gating tethers to open these channels in touch receptor neurons. To look closer, the authors used high-pressure freezing and serial-section immunoelectron microscopy. Antibodies against MeT channel subunits showed distinct puncta along the processes of touch receptor neurons. These puncta were in distinct, but overlapping, domains compared to collagen associated with the putative microtubular gating tethers. Many channel puncta were >5 nm from the nearest filament. However, the specialized microtubules were assembled in a cross-linked bundle that was connected by kinked filaments to the cell membrane. The authors suggest that this assembly converts external pressure into membrane stretch and thus facilitates MeT channel openings.
2. Early Auditory Circuit Assembly
Edmund J. Koundakjian, Jessica L. Appler, and Lisa V. Goodrich
Cochlear ganglion precursors in the otic vesicle express the transcription factor Neurogenin1 (Ngn1). Thus, Koundakjian et al. generated a transgenic mouse that expressed Ngn1-driven, tamoxifeninducible Cre recombinase so that they could follow the early development of cochlear ganglion neurons. Using low-dose tamoxifen to induce only sparse labeling with Cre, the authors identified isolated clusters (<12 cells) at postnatal day 0. These clusters were presumably descendents from a single precursor. Labeling at embryonic day 8.5 (E8.5) labeled the vestibular ganglion, whereas labeling at E12.5 labeled cochlear ganglion neurons. The latter included cells that innervate inner and outer hair cells. Tracking of labeled cells suggested that the peripheral processes first extended toward cues in the sensory epithelium and then Type I headed toward still immature inner hair cells while Type II headed toward immature outer hair cells. Central cochlear ganglion axons were topographically organized in the brainstem by E15.5, also before the cochlear nucleus was mature.
3. Faces, Places, and Twins
Thad A. Polk, Joonkoo Park, Mason R. Smith, and Denise C. Park
Everyone knows that monozygotic (MZ) twins look alike, but do their brains respond the same to stimuli" Polk et al. used functional MRI to compare the responses of twins to faces, places, or “pseudowords.” These stimuli were chosen because they evoke reproducible patterns of activity in the ventral visual cortex. Control images consisted of the same images in which the phase was scrambled (see figure). The authors compared pairs of MZ twins with pairs of dizygotic (DZ) twins. Subjects were presented with matching tasks for paired images of each type of stimulus. The neural activation patterns for faces and houses were more similar in MZ than DZ twins, but there was not a difference in the responses to pseudowords or chairs. Because the differences were confined to a subset of stimulus categories, the results could not be simply attributed to a higher degree of anatomical similarity in MZ twins. It’s in the genes, somewhere.
4. A Mouse Model of a Human Motor Neuron Disease
Chen Lai, Xian Lin, Jayanth Chandran, Hoon Shim, Wan-Jou Yang, and Huaibin Cai
Motor neurons are particularly vulnerable to problems in cargo transport along axons. This job is handled in the anterograde direction by kinesin and in the retrograde direction by the dynein/dynactin complex. This week, Lai et al. focused on dynactin P150glued, which is part of the dynactin complex that binds to microtubules and dynein and thus facilitates retrograde transport. A mutation in P150glued, G59S, has been linked to a familial form of motor neuron disease. The authors created a knock-in mouse model of this mutation, as well as heterozygous P150glued knock-out mice. The heterozygous knock-out mice were normal, but heterozygous knock-in mice had loss of motor neurons, gait abnormalities, and accumulations of neurofilaments and synaptic vesicles proteins at the neuromuscular junction. The results confirm the role of P150glued in retrograde transport and are consistent with the clinical picture of humans with this mutation.
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