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TGIF , a gene associated with human brain defects, regulates neuronal development
Author(s) -
Knepper Jessica L.,
James Alison C.,
Ming Jeffrey E.
Publication year - 2006
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.20725
Subject(s) - biology , neural tube , transcription factor , missense mutation , retinoic acid , pou domain , microbiology and biotechnology , gene , homeobox , genetics , phenotype , embryo
5′‐TG‐3′‐interacting factor (TGIF) is an atypical homeodomain protein. In vitro studies have shown that TGIF can repress transcription mediated by either of two signaling pathways: TGF‐β and retinoic acid signaling. Mutations in TGIF have been detected in patients with holoprosencephaly (HPE), a severe brain malformation associated with mental retardation. Thus, TGIF must play an essential role in nervous system development. However, the precise function of TGIF during vertebrate neural development is unknown. To investigate the in vivo role of TGIF, we overexpressed TGIF in the developing chick neural tube. Overexpressed TGIF decreased expression of specific genes expressed in dorsally restricted domains of the neural tube, including Cath1 , Msx2 , Pax6 , and Wnt1 . In contrast, the expression of other transcription factors, including those necessary for ventral fate such as Nkx2.2 , was not affected. Furthermore, a missense mutation in TGIF identified in an HPE patient disrupted the activity of TGIF. In addition, the related protein TGIF2 did not demonstrate the same activity as TGIF. Our data suggest that TGIF plays an important role in regulating the expression of genes expressed in specific dorsal–ventral domains during neural development. Developmental Dynamics 235:1482–1490, 2006. © 2006 Wiley‐Liss, Inc.

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