Functions of TGIF homeodomain proteins and their roles in normal brain development and holoprosencephaly. Am J Med Genet C Semin Med Genet 2018 Jun;178(2):128-139
Date
05/12/2018Pubmed ID
29749689Pubmed Central ID
PMC6125192DOI
10.1002/ajmg.c.31612Scopus ID
2-s2.0-85046830932 (requires institutional sign-in at Scopus site) 12 CitationsAbstract
Holoprosencephaly (HPE) is a frequent human forebrain developmental disorder with both genetic and environmental causes. Multiple loci have been associated with HPE in humans, and potential causative genes at 14 of these loci have been identified. Although TGIF1 (originally TGIF, for Thymine Guanine-Interacting Factor) is among the most frequently screened genes in HPE patients, an understanding of how mutations in this gene contribute to the pathogenesis of HPE has remained elusive. However, mouse models based on loss of function of Tgif1, and the related Tgif2 gene, have shed some light on how human TGIF1 variants might cause HPE. Functional analyses of TGIF proteins and of TGIF1 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. Although, some developmental processes that are regulated by TGIFs may be Nodal-dependent, it appears that the forebrain patterning defects and HPE in Tgif mutant mouse embryos is primarily due to altered signaling via the Shh pathway.
Author List
Wotton D, Taniguchi KAuthor
Kenichiro Taniguchi PhD Assistant Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsBody Patterning
Brain
Craniofacial Abnormalities
Developmental Disabilities
Disease Models, Animal
Disease Susceptibility
Gene Deletion
Gene Expression Regulation
Genetic Variation
Holoprosencephaly
Homeodomain Proteins
Humans
Mice
Nodal Protein
Organogenesis
Prosencephalon
Repressor Proteins
Signal Transduction
Transcription, Genetic
