- Library Home /
- Search Collections /
- Open Collections /
- Browse Collections /
- UBC Theses and Dissertations /
- Role of TGIF in cell cycle control and establishment...
Open Collections
UBC Theses and Dissertations
UBC Theses and Dissertations
Role of TGIF in cell cycle control and establishment of laterality Mar, Lynn
Abstract
Holoprosencephaly (HPE) is the most common structural anomaly of the human brain, resulting from incomplete cleavage of the developing forebrain during embryogenesis. Haploinsufficient mutations in TG-Interacting Factor (TGIF) were previously identified in a subset of HPE families and sporadic patients, and this gene is located within a region of Chromosome 18 that is associated with non-random chromosomal aberrations in HPE patients. TGIF is a transcription factor that contains a three amino acid loop extension (TALE) homeodomain and functions both as a co-repressor of the TGF-β pathway and as a competitor of the retinoic acid pathway. Mice made deficient for Tgif exhibited laterality defects and growth retardation, and developed kinked tails. Analysis of Tgif⁻ʹ⁻ mouse embryonic fibroblasts (MEFs) in vitro demonstrated that Tgif regulates proliferation and progression through the G₁ cell cycle phase. Wild-type human TGIF was able to rescue this proliferative defect in MEFs. In contrast, a subset of human Tgif mutations detected in HPE patients was unable to rescue the proliferative defect. However, an absence of Tgif did not alter the normal inhibition of proliferation caused by treatment with TGF-β or retinoic acid. Developmental control of proliferation by Tgif may play a role in the pathogenesis of HPE.
Item Metadata
Title |
Role of TGIF in cell cycle control and establishment of laterality
|
Creator | |
Publisher |
University of British Columbia
|
Date Issued |
2006
|
Description |
Holoprosencephaly (HPE) is the most common structural anomaly of the human brain, resulting from incomplete cleavage of the developing forebrain during embryogenesis. Haploinsufficient mutations in TG-Interacting Factor (TGIF) were previously identified in a subset of HPE families and sporadic patients, and this gene is located within a region of Chromosome 18 that is associated with non-random chromosomal aberrations in HPE patients. TGIF is a transcription factor that contains a three amino acid loop extension (TALE) homeodomain and functions both as a co-repressor of the TGF-β pathway and as a competitor of the retinoic acid pathway. Mice made deficient for Tgif exhibited laterality defects and growth retardation, and developed kinked tails. Analysis of Tgif⁻ʹ⁻ mouse embryonic fibroblasts (MEFs) in vitro demonstrated that Tgif regulates proliferation and progression through the G₁ cell cycle phase. Wild-type human TGIF was able to rescue this proliferative defect in MEFs. In contrast, a subset of human Tgif mutations detected in HPE patients was unable to rescue the proliferative defect. However, an absence of Tgif did not alter the normal inhibition of proliferation caused by treatment with TGF-β or retinoic acid. Developmental control of proliferation by Tgif may play a role in the pathogenesis of HPE.
|
Genre | |
Type | |
Language |
eng
|
Date Available |
2010-01-17
|
Provider |
Vancouver : University of British Columbia Library
|
Rights |
For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.
|
DOI |
10.14288/1.0092936
|
URI | |
Degree | |
Program | |
Affiliation | |
Degree Grantor |
University of British Columbia
|
Campus | |
Scholarly Level |
Graduate
|
Aggregated Source Repository |
DSpace
|
Item Media
Item Citations and Data
Rights
For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.