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Expression and functional analysis of Tgif during mouse midline development
Author(s) -
Jin JiuZhen,
Gu Shi,
McKinney Patrick,
Ding Jixiang
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.20642
Subject(s) - biology , forebrain , homeobox , neural development , neural plate , microbiology and biotechnology , neural tube , neuroectoderm , floor plate , anatomy , embryonic stem cell , neuroscience , gene , genetics , embryo , transcription factor , central nervous system , mesoderm
Abstract The Tgif gene encodes a homeodomain protein that functions as a transforming growth factor beta (TGF‐β) repressor by binding to Smad2. Mutations in the TGIF gene are associated with human holoprosencephaly, a common birth defect caused by the failure of anterior ventral midline formation. However, Smad2‐mediated TGF‐β signaling in the axial mesendoderm has been demonstrated to be essential for ventral midline formation, and loss of a Smad2 antagonist should in principle promote rather than inhibit ventral midline formation. This suggests a more complex mechanism for the function of TGIF in controlling ventral midline formation. To explore the role of TGIF in ventral forebrain formation and patterning, we investigated Tgif expression and function during mouse development by in situ hybridization and gene targeting. We found that Tgif is highly expressed in the anterior neural plate, consistent with the proposed neural differentiation model in which TGF‐β suppression is required for normal neural differentiation. This result suggests a possible role for Tgif in anterior neural differentiation and patterning. However, targeted disruption of the Tgif gene during mouse development does not cause any detectable defects in development and growth. Both histological examination and gene expression analysis showed that Tgif −/− embryos have a normal ventral specification in the central nervous system, including the forebrain region. One interpretation of these results is that the loss of TGIF function is compensated by other TGF‐β antagonists such as c‐Ski and SnoN during vertebrate anterior neural development. Developmental Dynamics 235:547–553, 2006. © 2005 Wiley‐Liss, Inc.