Lineage Is a Poor Predictor of Interneuron Positioning within the Forebrain

Abstract

This Matters Arising Response paper addresses the Sultan etal. (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 etal. (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 etal. to a random computer simulation, Sultan etal. suggest that clonally related interneurons are "not randomly dispersed." We argue thatthis comparison provides no insight into the influence of clonality on interneuron development because theentire population of cortical interneurons is "not randomly dispersed" invivo. We find that the majorityof 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.