<it>Ascl1 </it>is a required downstream effector of <it>Gsx </it>gene function in the embryonic mouse telencephalon

<p>Abstract</p> <p>Background</p> <p>The homeobox gene <it>Gsx2 </it>(formerly <it>Gsh2</it>) is known to regulate patterning in the lateral ganglionic eminence (LGE) of the embryonic telencephalon. In its absence, the closely related gene <it>Gsx1 </it>(previously known as <it>Gsh1</it>) can partially compensate in the patterning and differentiation of ventral telencephalic structures, such as the striatum. However, the cellular and molecular mechanisms underlying this compensation remain unclear.</p> <p>Results</p> <p>We show here that in the <it>Gsx2 </it>mutants Gsx1 is expressed in only a subset of the ventral telencephalic progenitors that normally express Gsx2. Based on the similarities in the expression of Gsx1 and Ascl1 (Mash1) within the <it>Gsx2 </it>mutant LGE, we examined whether Ascl1 plays an integral part in the <it>Gsx1</it>-based recovery. <it>Ascl1 </it>mutants show only modest alterations in striatal development; however, in <it>Gsx2;Ascl1 </it>double mutants, striatal development is severely affected, similar to that seen in the <it>Gsx1;Gsx2 </it>double mutants. This is despite the fact that <it>Gsx1 </it>is expressed, and even expands, in the <it>Gsx2;Ascl1 </it>mutant LGE, comparable to that seen in the <it>Gsx2 </it>mutant. Finally, Notch signaling has recently been suggested to be required for normal striatal development. In spite of the fact that Notch signaling is severely disrupted in <it>Ascl1 </it>mutants, it actually appears to be improved in the <it>Gsx2;Ascl1 </it>double mutants.</p> <p>Conclusion</p> <p>These results, therefore, reveal a non-proneural requirement of <it>Ascl1 </it>that together with <it>Gsx1 </it>compensates for the loss of <it>Gsx2 </it>in a subset of LGE progenitors.</p