Different activity patterns control various stages of Reelin synthesis in the developing neocortex

Abstract

Reelin is a large extracellular matrix protein abundantly expressed in the developing neocortex of mammals. During embryonic and early postnatal stages in mice, Reelin is secreted by a transient neuronal population, the Cajal–Retzius neurons (CRs), and is mostly known to insure the inside-out migration of neurons and the formation of cortical layers. During the first 2 postnatal weeks, CRs disappear from the neocortex and a subpopulation of GABAergic neurons takes over the expression of Reelin, albeit in lesser amounts. Although Reelin expression requires a tight regulation in a time- and cell-type specific manner, the mechanisms regulating the expression and secretion of this protein are poorly understood. In this study, we establish a cell-type specific profile of Reelin expression in the marginal zone of mice neocortex during the first 3 postnatal weeks. We then investigate whether electrical activity plays a role in the regulation of Reelin synthesis and/or secretion by cortical neurons during the early postnatal period. We show that increased electrical activity promotes the transcription of reelin via the brain-derived neurotrophic factor/TrkB pathway, but does not affect its translation or secretion. We further demonstrate that silencing the neuronal network promotes the translation of Reelin without affecting the transcription or secretion. We conclude that different patterns of activity control various stages of Reelin synthesis, whereas its secretion seems to be constitutive.

Reelin, neocortex, development, neuronal activity, neurotrophic signaling