The roles of integrin subunits and intracellular molecules in regulating the migration and neuritogenesis of neurons isolated from 16.5 gestation days rat fetal cortices were examined using in vitro assays. Results showed that laminin supported the migration of fetal cortical neurons better than fibronectin and that the fetal cortical neurons migrated on laminin using β1 and α3 integrin subunits which make up the α3β1 integrin receptor. On fibronectin, the migration was mediated by β1 integrin subunit. Perturbation of src kinase, phospholipase C, or protein kinase C activity, inhibition of IP3 receptor mediated calcium release, or chelation of intracellular calcium inhibited both migration and neuritogenesis, whereas inhibition of growth factor signaling via MEK inhibited only the neuritogenesis. The detection of α1 and α9 transcripts suggested that the migration of fetal cortical neurons may also be mediated by α1β1 and α9β1 integrin receptors. Results showed that calcium may regulate migration and neuritogenesis by maintaining optimum levels of microtubules in the fetal cortical neurons. It is concluded that the fetal cortical neurons are fully equipped with the integrin signaling cascade required for their migration and neuritogenesis, whereas crosstalk between the integrin and growth-factor signaling regulate only the neuritogenesis. 1. Introduction During brain development, postmitotic neurons migrate from their site of origin to distant places, differentiate, and make connections forming different layers of the cortex. Defects in this process results in abnormal neuronal positioning and connections in the brain, which may cause neurobehavioral problems later in life [1]. Neuritogenesis, an early step of neuron differentiation, is the synthesis of multiple growth cone tipped extensions (neurites) that ultimately form the axons and dendrites of neurons [2]. Mechanisms that regulate the migration and differentiation of neurons are not fully understood. Cell surface integrin receptors, each consisting of an α and a β subunit, play critical roles in the glial-guided migration of neurons in the brain [3]. The extracellular domains of the receptor subunits bind with extracellular matrix (ECM) proteins (such as fibronectin and laminin) and the cytosolic domains of β subunits interact with kinases, adaptor molecules, and the cytoskeleton [4]. These interactions facilitate the “outside-in” and the “inside-out” signaling across the cell membrane by the integrin heterodimers [5] that may lead to cell migration and neuritogenesis [6]. Integrin receptors with
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