Astrocyte-encoded positional cues maintain sensorimotor circuit integrity

• Published in: Nature (London) Vol. 509; no. 7499; pp. 189 - 194
• Main Authors: Molofsky, Anna V., Kelley, Kevin W., Tsai, Hui-Hsin, Redmond, Stephanie A., Chang, Sandra M., Madireddy, Lohith, Chan, Jonah R., Baranzini, Sergio E., Ullian, Erik M., Rowitch, David H.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 08-05-2014; Nature Publishing Group
• Subjects: 13/106; 13/51; 14/1; 14/19; 38/61; 38/77; 42/35; 631/378/2571/219; 64/110; 64/60; 96/31; Animals; Astrocytes; Astrocytes - cytology; Astrocytes - physiology; Axons - physiology; Cell Polarity; Cell Survival - drug effects; Central nervous system; Heterogeneity; Humanities and Social Sciences; Humans; Medical research; Mice; Motor Neurons - cytology; Motor Neurons - drug effects; Motor Neurons - physiology; multidisciplinary; Neural circuitry; Neural Pathways - physiology; Neurological research; Neurology; Neurons; Perceptual-motor processes; Physiological aspects; Proteins; Science; Semaphorin-3A - deficiency; Semaphorin-3A - genetics; Semaphorin-3A - metabolism; Semaphorin-3A - pharmacology; Sensory Receptor Cells - cytology; Sensory Receptor Cells - physiology; Spinal cord; Spinal Cord - cytology; Synapses - metabolism; United States
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature13161

Astrocytes, the most abundant cells in the central nervous system, promote synapse formation and help to refine neural connectivity. Although they are allocated to spatially distinct regional domains during development, it is unknown whether region-restricted astrocytes are functionally heterogeneous. Here we show that postnatal spinal cord astrocytes express several region-specific genes, and that ventral astrocyte-encoded semaphorin 3a (
Sema3a
) is required for proper motor neuron and sensory neuron circuit organization. Loss of astrocyte-encoded
Sema3a
leads to dysregulated α-motor neuron axon initial segment orientation, markedly abnormal synaptic inputs, and selective death of α- but not of adjacent γ-motor neurons. In addition, a subset of TrkA
+
sensory afferents projects to ectopic ventral positions. These findings demonstrate that stable maintenance of a positional cue by developing astrocytes influences multiple aspects of sensorimotor circuit formation. More generally, they suggest that regional astrocyte heterogeneity may help to coordinate postnatal neural circuit refinement.
Populations of astrocytes in the spinal cord are shown to express region-specific genes, with ventral astrocyte-encoded Sema3a necessary for proper motor neuron circuit organization and typical sensory afferent projection patterns; these findings suggest that astrocytes provide a positional cue for maintaining proper circuit formation and refinement.
Positioning role for local astrocytes in development
Astrocytes are widely recognized as regulators of synapse formation in the central nervous system, and recent work showed that they tend to remain in distinct regions during development. It was not known whether regional populations of astrocyte were similar or distinct or how any differences might affect synaptic development. Here, David Rowitch and colleagues determine that local populations of astrocytes in the spinal cord can express region-specific genes, with ventral astrocyte-encoded
Sema3a
necessary for proper motor neuron circuit organization and typical sensory afferent projection patterns. The argument is made that these astrocytes provide a positional cue to maintain proper circuit formation and refinement.