Intragenic deletion of Tgif causes defectsin brain development.

@article{Kuang2006IntragenicDO,
  title={Intragenic deletion of Tgif causes defectsin brain development.},
  author={Chenzhong Kuang and Yan Xiao and Ling Yang and Qian Chen and Zhenzhen Wang and Simon J. Conway and Yan Chen},
  journal={Human molecular genetics},
  year={2006},
  volume={15 24},
  pages={
          3508-19
        }
}
TG-interacting factor (TGIF) is a homeodomain-containing protein and functions as a transcriptional repressor within the TGF-beta and retinoic acid signaling pathways. Heterozygous mutations of TGIF have been found in patients with holoprosencephaly (HPE), which is the most common congenital brain malformation in humans. However, targeted null deletions of the entire Tgif gene in mice surprisingly revealed no apparent brain defects. We report here that deletion of the third exon of Tgif gene… 
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Loss of Tgif Function Causes Holoprosencephaly by Disrupting the Shh Signaling Pathway
TLDR
Results support a model in which Tgif function limits Nodal signaling to maintain the appropriate output of the Shh pathway in the forebrain, and show for the first time that Tgif1 mutation in mouse contributes to HPE pathogenesis.
Functions of TGIF homeodomain proteins and their roles in normal brain development and holoprosencephaly
TLDR
Functional analyses of TGIF proteins and ofTGIF1 single nucleotide variants from HPE patients, combined with analysis of forebrain development in mouse embryos lacking both Tgif1 and Tgif2, suggest that TGIFs regulate the transforming growth factor ß/Nodal signaling pathway and sonic hedgehog (SHH) signaling independently.
Tgif1 and Tgif2 Regulate Axial Patterning in Mouse
TLDR
It is shown that in mice of a relatively pure C57BL/6 strain background, loss of Tgif1 alone results in defective axial patterning and altered expression of Hoxc6, and that reduced TGIF function sensitizes embryos to the effects of retinoic acid.
Zebrafish model of holoprosencephaly demonstrates a key role for TGIF in regulating retinoic acid metabolism.
TLDR
It is demonstrated in zebrafish that Tgif plays a key role in regulating RA signaling, and is essential to properly pattern the forebrain, and a model in which Tgif controls forebrain patterning by regulating RA degradation is proposed.
Tgif1 and Tgif2 regulate Nodal signaling and are required for gastrulation
TLDR
Data show that T gif function is required for gastrulation, and provide the first clear evidence that Tgifs limit the transcriptional response to Nodal signaling during early embryogenesis.
Transgenic analyses of TGIF family proteins in Drosophila imply their role in cell growth.
Role of transcription factor Tgif2 in photoreceptor differentiation in the mouse retina.
Generation of novel conditional and hypomorphic alleles of the Smad2 gene
TLDR
This work utilized the Cre‐loxP system to generate a conditional allele which functions hypomorphically when placed opposite a null allele, and unlike the other published Smad2 hypomorphic allele, can be maintained in the homozygous state.
Gli2 gene-environment interactions contribute to the etiological complexity of holoprosencephaly: evidence from a mouse model
TLDR
It is demonstrated that mutations in Gli2, which encodes a Hedgehog pathway transcription factor, can cause or predispose to HPE depending upon gene dosage, and reveals a causative role for GLI2 in HPE genesis.
Murine models of holoprosencephaly.
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References

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TLDR
Overexpressed TGIF decreased expression of specific genes expressed in dorsally restricted domains of the neural tube, including Cath1, Msx2, Pax6, and Wnt1, and suggested that TGIF plays an important role in regulating the expression of genes expression in specific dorsal–ventral domains during neural development.
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TLDR
Cellular analysis of mutant mouse embryonic fibroblasts demonstrated for the first time that Tgif regulates proliferation and progression through the G1 cell cycle phase and a subset of human Tgif mutations detected in HPE patients was unable to rescue the proliferative defect.
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TLDR
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TLDR
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TLDR
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TLDR
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TLDR
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TLDR
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TLDR
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TLDR
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