Tulp3 Is a Critical Repressor of Mouse Hedgehog Signaling

被引：41

作者：

Cameron, Don A. ^{[1
,2
]}

Pennimpede, Tracie ^{[1
,3
]}

Petkovich, Martin ^{[1
,2
,3
]}

机构：

[1] Queens Univ, Canc Res Inst, Div Canc Biol & Genet, Kingston, ON K71 3N6, Canada

[2] Queens Univ, Canc Res Inst, Dept Biochem, Kingston, ON K71 3N6, Canada

[3] Queens Univ, Canc Res Inst, Dept Pathol & Mol Med, Kingston, ON K71 3N6, Canada

来源：

DEVELOPMENTAL DYNAMICS | 2009年 / 238卷 / 05期

关键词：

Tulp3; sonic hedgehog; neural patterning; limb development; INTRAFLAGELLAR TRANSPORT PROTEINS; TUBBY-LIKE PROTEIN-1; SONIC-HEDGEHOG; NEURAL-TUBE; VERTEBRATE LIMB; FLOOR PLATE; SPINAL-CORD; TRANSCRIPTION FACTORS; FUNCTIONAL-ANALYSIS; POLARIZING ACTIVITY;

D O I：

10.1002/dvdy.21926

中图分类号：

R602 [外科病理学、解剖学]; R32 [人体形态学];

学科分类号：

100101 ;

摘要：

Precise regulation of the morphogen sonic hedgehog (Shh) and modulation of the Shh signaling pathway is required for proper specification of cell fate within the developing limbs and neural tube, and resultant tissue morphogenesis. Tulp3 (tubby-like protein 3) is a protein of unknown function which has been implicated in nervous system development through gene knockout studies. We demonstrate here that mice lacking the Tulp3 gene develop abnormalities of both the neural tube and limbs consistent with improper regulation of Shh signaling. Tulp3(-/-) embryos show expansion of Shh target gene expression and display a ventralization of neural progenitor cells in the caudal neural tube. We further show that TuJp3(-/-)/Shh(-/-) compound mutant embryos resemble Tulp3 mutants, and express Shh target genes in the neural tube and limbs which are not expressed in Shh(-/-) embryos. This work uncovers a novel role for Tulp3 as a negative regulatory factor in the Rh pathway. Developmental Dynamics 238:1140-1149, 2009. (C) 2009 Wiley-Liss, Inc.

引用

页码：1140 / 1149

页数：10

共 57 条

[1] The retinoic acid-metabolizing enzyme, CYP26A1, is essential for normal hindbrain patterning, vertebral identity, and development of posterior structures [J].