Abstract
Patterning of the telencephalic neuroepithelium is a tightly regulated process controlled by transcription factors and signalling molecules. The cortical primordium is flanked by two signalling centres, the hem medially, and the antihem laterally. The hem induces the formation of the hippocampus in adjacent neuroepithelium. Therefore, the position of the hem defines the position of the hippocampus in the brain. The antihem is positioned at the boundary between the dorsal and ventral telencephalon and proposed to provide patterning cues during development.LIM-homeodomain (LIM-HD) transcription factor LHX2 suppresses both hem and antihem fate in the cortical neuroepithelium. Upon loss of Lhx2, medial cortical neuroepithelium is transformed into hem, whereas lateral cortical neuroepithelium is transformed into antihem. Here, we show that transcription factor PAX6, known to regulate patterning of the lateral telencephalon, restricts this tissue from transforming into hem upon loss of Lhx2. When Lhx2 and Pax6 are both deleted, the cortical hem expands to occupy almost the complete extent of the cortical primordium, indicating that both factors act to suppress hem fate in the lateral telencephalon. Furthermore, the shift in the pallial-subpallial boundary and absence of the antihem, observed in the Pax6 mutant, are both restored in the Lhx2; Pax6 double mutant.Together, these results not only reveal a novel function for LHX2 in regulating dorsoventral patterning in the telencephalon, but also identify PAX6 as a fundamental regulator of where the hem can form, and therefore implicate this molecule as a determinant of hippocampal positioning.
Highlights
In development, tissues are patterned by the action of morphogens secreted by signaling centers known as “organizers.” The WNT- and BMP- secreting cortical hem in the telencephalon is one such medial signaling center [1, 2]
In the Lhx2 null mutant, the cortical primordium cannot retain its identity, but is transformed into two alternate fates: medial cortical neuroepithelium is transformed into hem, whereas lateral cortical neuroepithelium is transformed into antihem [4, 5]
When we examined the lateral telencephalon of embryos that displayed complete recombination of Pax6 but had some unrecombined patches of Lhx2, it was apparent that hem only formed where both genes were lacking (Fig. 3f)
Summary
Tissues are patterned by the action of morphogens secreted by signaling centers known as “organizers.” The WNT- and BMP- secreting cortical hem in the telencephalon is one such medial signaling center [1, 2]. At the lateral edge of the cortical neuroepithelium, the EGF-expressing antihem defines the boundary between the dorsal and ventral telencephalon [3]. The factors that act to restrict the hem to its position at the medial edge of the cortical neuroepithelium are critical determinants of where the hippocampus. Pax is expressed in a lateral(high)medial(low) gradient, opposite to that of Lhx2 [6, 7]. We hypothesized that the presence of PAX6 may restrict the medio-lateral extent of the hem in Lhx
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