Lineage Is a Poor Predictor of Interneuron Positioning within the Forebrain

This Matters Arising Response paper addresses the Sultan et al. (2016) Matters Arising paper, published concurrently in Neuron. Clonally related excitatory neurons maintain a coherent relationship following their specification and migration. Whether cortical interneurons behave similarly is a fundamental question in developmental neuroscience. In Mayer et al. (2015), we reported that sibling interneurons disperse over several millimeters, across functional and anatomical boundaries. This finding demonstrated that clonality is not predictive of an interneuron's ultimate circuit specificity. Comparing the distribution of interneurons published in Mayer et al. to a random computer simulation, Sultan et al. suggest that clonally related interneurons are "not randomly dispersed." We argue that this comparison provides no insight into the influence of clonality on interneuron development because the entire population of cortical interneurons is "not randomly dispersed" in vivo. We find that the majority of cortical interneurons are similarly distributed whether or not they share a lineal relationship. Thus, at present there is no compelling evidence that clonality influences the position or function of interneurons.