NDLI: Tubby-like protein 3 (TULP3) regulates patterning in the mouse embryo through inhibition of Hedgehog signaling

Content Provider	PubMed Central
Author	Norman, Ryan X. Ko, Hyuk W. Huang, Viola Eun, Christine M. Abler, Lisa L. Zhang, Zhen Sun, Xin Eggenschwiler, Jonathan T.
Copyright Year	2009
Abstract	Tubby-like protein 3 (TULP3) is required for proper embryonic development in mice. Disruption of mouse Tulp3 results in morphological defects in the embryonic craniofacial regions, the spinal neural tube and the limbs. Here, we show that TULP3 functions as a novel negative regulator of Sonic hedgehog (Shh) signaling in the mouse. In Tulp3 mutants, ventral cell types in the lumbar neural tube, which acquire their identities in response to Shh signaling, are ectopically specified at the expense of dorsal cell types. Genetic epistasis experiments show that this ventralized phenotype occurs independently of Shh and the transmembrane protein Smoothened, but it is dependent on the transcription factor Gli2. The ventralized phenotype is also dependent on the kinesin II subunit Kif3A, which is required for intraflagellar transport and ciliogenesis. In addition, TULP3 is required for proper Shh-dependent limb patterning and for maintaining the correct balance between differentiation and proliferation in the neural tube. Finally, the localization of TULP3 to the tips of primary cilia raises the possibility that it regulates the Hedgehog pathway within this structure.
Related Links	http://dx.doi.org/10.1093/hmg/ddp113
Ending Page	1754
Page Count	15
Starting Page	1740
File Format	PDF
ISSN	09646906
e-ISSN	14602083
Journal	Human Molecular Genetics
Issue Number	10
Volume Number	18
Language	English
Publisher	Oxford University Press
Publisher Date	2009-05-15
Access Restriction	Open
Rights Holder	Oxford University Press
Subject Keyword	Genetics(clinical) Genetics Molecular Biology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Genetics Molecular Biology Genetics (clinical)

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Tubby-like protein 3 (TULP3) regulates patterning in the mouse embryo through inhibition of Hedgehog signaling

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Tubby-like protein 3 (TULP3) regulates patterning in the mouse embryo through inhibition of Hedgehog signaling

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