The E2A splice variant E47 regulates the differentiation of projection neurons via p57(KIP2) during cortical development.

During corticogenesis, distinct classes of neurons are born from progenitor cells located in the ventricular and subventricular zones, from where they migrate towards the pial surface to assemble into highly organized layer-specific circuits. However, the precise and coordinated transcriptional network activity defining neuronal identity is still not understood. Here, we show that genetic depletion of the basic helix-loop-helix (bHLH) transcription factor E2A splice variant E47 increased the number of Tbr1-positive deep layer and Satb2-positive upper layer neurons at E14.5, while depletion of the alternatively spliced E12 variant did not affect layer-specific neurogenesis. While ChIP-Seq identified a big overlap for E12- and E47-specific binding sites in embryonic NSCs, including sites at the cyclin-dependent kinase inhibitor (CDKI) Cdkn1c gene locus, RNA-Seq revealed a unique transcriptional regulation by each splice variant. E47 activated the expression of the CDKI Cdkn1c through binding to a distal enhancer. Finally, overexpression of E47 in embryonic NSCs in vitro impaired neurite outgrowth and E47 overexpression in vivo by in utero electroporation disturbed proper layer-specific neurogenesis and upregulated p57(KIP2) expression. Overall, this study identified E2A target genes in embryonic NSCs and demonstrates that E47 regulates neuronal differentiation via p57(KIP2)

The Kalahari Craton during the assembly and dispersal of Rodinia

In this paper, we review the dimensions, geometry and architecture of the components of the Kalahari Craton and the various positions this important crustal block could have occupied within Rodinia. The Kalahari Craton was spawned from a small composite Archaean core which grew by prolonged crustal accretion in the Palaeoproterozoic along its NW side (Magondi–Okwa–Kheis Belt, Rehoboth Subprovince) to form the Proto-Kalahari Craton by 1750 Ma. From ca. 1400 to 1000 Ma, all margins of this crustal entity recorded intense tectonic activity: the NW margin was a major active continental margin between ca. 1400 and 1200 Ma and along the southern and eastern margins, the Namaqua–Natal–Maud–Mozambique Belt records a major arc–accretion and continent–collision event between ca. 1100 and 1050 Ma. By ca. 1050 Ma, the Proto-Kalahari nucleus was almost completely rimmed by voluminous Mesoproterozoic crust and became a larger entity, the Kalahari Craton. Apart from southern Africa, fragments of the Kalahari Craton are now exposed in East- and West-Antarctica, the Falkland Islands and possibly also in South America. Immediately prior to the onset of arc– and continent–continent collision along the Namaqua–Natal–Maud Belt (part of the widespread “Grenville-age” orogeny during which Rodinia was assembled), Kalahari was subjected to intraplate magmatism – the Umkondo–Borg Large Igneous Province – at ca. 1110 Ma. The post-Rodinia rift and drift history of the Kalahari Craton is best preserved along the western, south-western and north-western margin, where rift sediments and volcanics indicate rifting and break-up at ca. 800–750 Ma. The position of the Kalahari Craton in Rodinia is problematic, and there is no unique solution for its placement in the supercontinent. One set of models has the Kalahari Craton lying along the SW side of Laurentia with the Namaqua–Natal–Maud Belt facing either inboard (correlation with the Ottawan cycle of the Grenville orogen) or outboard (mainly for palaeomagnetic reasons). In this arrangement the relatively late rift history and the subsequent incorporation of Kalahari into Gondwana is problematic. Alternatively, Kalahari could have been attached to Western Australia. In this model the Namaqua–Natal–Maud Belt has no counterpart and, although the timing of rifting at ca. 750 Ma fits, the location of rifting is problematic—the Kalahari Craton would have had to undergo major rifting along its eastern, rather than its western side, which is not consistent with overservations. So the matter is as yet unresolved, and much of the evidence of rifting along the eastern side of the Kalahari Craton was obliterated due to high-grade overprint along the Late Neoproterozoic/Early Palaeozoic East African–Antarctic Orogen