Abstract
ABSTRACTDuring forebrain development, a telencephalic organizer called the cortical hem is crucial for inducing hippocampal fate in adjacent cortical neuroepithelium. How the hem is restricted to its medial position is therefore a fundamental patterning issue. Here, we demonstrate that Foxg1-Lhx2 interactions are crucial for the formation of the hem. Loss of either gene causes a region of the cortical neuroepithelium to transform into hem. We show that FOXG1 regulates Lhx2 expression in the cortical primordium. In the absence of Foxg1, the presence of Lhx2 is sufficient to suppress hem fate, and hippocampal markers appear selectively in Lhx2-expressing regions. FOXG1 also restricts the temporal window in which loss of Lhx2 results in a transformation of cortical primordium into hem. Therefore, Foxg1 and Lhx2 form a genetic hierarchy in the spatiotemporal regulation of cortical hem specification and positioning, and together ensure the normal development of this hippocampal organizer.
Highlights
The cortical primordium gives rise to the entire cerebral cortex, including both neocortex and hippocampus
Administering tamoxifen to CreER;Lhx2lox/lox mice at E8.5 results in a phenotype that closely approximates that seen in Lhx2-null embryos in which the hem and anti-hem are both expanded and are seen juxtaposed to each other in the dorsal telencephalon, and no cortical primordium is detectable (Fig. 1F-J) (Mangale et al, 2008)
We chose E8.5 as the starting point for our analysis of loss of Lhx2, and E10.5 as the endpoint, as we and others had established in earlier work that loss of Lhx2 after E10.5 does not result in expansion of the hem (Mangale et al, 2008; Chou et al, 2009)
Summary
The cortical primordium gives rise to the entire cerebral cortex, including both neocortex and hippocampus. Loss of Foxg1 spares only medial-dorsal fates, so the telencephalon contains an expanded hem and some hippocampal primordium, but no lateral cortical tissue or antihem (Vyas et al, 2003; Muzio and Mallamaci, 2005).
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