Journal
DEVELOPMENTAL BIOLOGY
Volume 257, Issue 2, Pages 343-355Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/S0012-1606(03)00065-4
Keywords
gli3; shh; BMP; neural; chick; spinal cord; patterning; Pallister Hall Syndrome
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A concentration gradient of Shh is thought to pattern the ventral neural tube, and these ventral cell types are absent in shh(-/-) mice. Based on in vitro and genetic studies, the zinc finger-containing transcription factors Gli 1, 2, and 3 are mediators of the Shh intracellular response. The floorplate and adjacent cell types are absent in glil(-/-);gli2(-/-) mice, but part of the Shh(-/-) phenotype in the neural tube is alleviated in the Shh(-/-);gli3(-/-) double mutant. This is consistent with the predicted role of Gli3 as a repressor of the Shh response. Gli3 repressor activity is blocked by Shh. In order to test the role of the repressor form of Gli3 in the neural tube, a truncated version of Gli3 (Gli3R*) was designed to mimic a Pallister Hall allele. Gli3R* acts as a constitutive repressor independent of Shh signaling. Misexpression of Gli3R* in the chick neural tube caused a ventral expansion of class-I, dorsal progenitor proteins and a loss of class-II, ventral progenitor proteins consistent with expected activity as a repressor of the Shh response. Activation of the BMP response is sufficient to maintain gli3 expression in neural plate explants, which might be a mechanism by which BMPs antagonize the Shh response. (C) 2003 Elsevier Science (USA). All rights reserved.
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