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Er81 is a downstream target of Pax6 in cortical progenitors

DOI: 10.1186/1471-213x-8-23

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Abstract:

We identified and analyzed the regulatory function of an evolutionarily conserved upstream DNA sequence in the putative mouse Er81 promoter. Three potential Pax6 binding sites were identified in this region. We found that the presence of one of these sites is necessary and sufficient for full activation of the Er81 promoter in Pax6-transfected HeLa cells, while other still unknown factors appear to contribute to Er81 promoter activity in cortical progenitors and neuronal cells. The results suggest that endogenous Pax6, which is expressed at the highest level in progenitors of the rostrolateral cortex, exerts region-specific control of Er81 activity, thus specifying a subpopulation of layer 5 projection neurons.We conclude that the genetic interplay between the transcription factors, Pax6 and Er81, is responsible, in part, for the regional specification of a distinct sublineage of layer 5 projection neurons.In the mammalian neocortex (pallium), neurons with striking morphological and functional diversity are organized radially in six layers, and tangentially into numerous functional domains. Only recently have the molecular and cellular mechanisms that guide the process of corticogenesis responsible for this organization begun to be resolved [1,2]. The main source of cortical projection neurons is the population of pluripotent radial glial progenitors (RG), which divide asymmetrically at the apical surface of the ventricular zone (VZ) and generate both neuronal and glial progeny [3]. After midgestation, RG generate neuronal progenitors, termed intermediate or basal progenitors (BPs), that divide symmetrically at the basal surface of the VZ and in the subventricular zone (SVZ). Thus, while the asymmetric division of RG progenitors gives rise to progeny with distinct cell fates, the symmetric division of BPs primarily modulates the number of cells in previously established neuronal cell lineages [4]. The projection neurons of the lower (6 and 5) and upper (4–2) layers

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