Ascl1 is a required downstream effector of Gsx gene function in the embryonic mouse telencephalon.
BACKGROUND
The homeobox gene Gsx2 (formerly Gsh2) is known to regulate patterning in the lateral ganglionic eminence (LGE) of the embryonic telencephalon. In its absence, the closely related gene Gsx1 (previously known as Gsh1) 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.


RESULTS
We show here that in the Gsx2 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 Gsx2 mutant LGE, we examined whether Ascl1 plays an integral part in the Gsx1-based recovery. Ascl1 mutants show only modest alterations in striatal development; however, in Gsx2;Ascl1 double mutants, striatal development is severely affected, similar to that seen in the Gsx1;Gsx2 double mutants. This is despite the fact that Gsx1 is expressed, and even expands, in the Gsx2;Ascl1 mutant LGE, comparable to that seen in the Gsx2 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 Ascl1 mutants, it actually appears to be improved in the Gsx2;Ascl1 double mutants.


CONCLUSIONS
These results, therefore, reveal a non-proneural requirement of Ascl1 that together with Gsx1 compensates for the loss of Gsx2 in a subset of LGE progenitors.
Wang
Bei
B
Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati OH 45229, USA. bei.wang@ucsf.edu
Waclaw
Ronald R
RR
Allen
Zegary J
ZJ
Guillemot
Francois
F
Campbell
Kenneth
K
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D003342:Corpus Striatum / Q000196:embryology / Q000378:metabolism*; D004622:Embryo, Mammalian; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D016133:Polymerase Chain Reaction; D013687:Telencephalon / Q000196:embryology / Q000378:metabolism*
D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; C499317:Ascl1 protein, mouse; C098513:Gsh1 protein, mouse; C109498:Gsh2 protein, mouse