The basic helix-loop-helix transcription factor Hand1 regulates mouse development as a homodimer

Hu, Dong, Scott, Ian C., Snider, Fran, Geary-Joo, Colleen, Zhao, Xiang, Simmons, David G. and Cross, James C. (2013) The basic helix-loop-helix transcription factor Hand1 regulates mouse development as a homodimer. Developmental Biology, 382 2: 470-481. doi:10.1016/j.ydbio.2013.07.025


Author Hu, Dong
Scott, Ian C.
Snider, Fran
Geary-Joo, Colleen
Zhao, Xiang
Simmons, David G.
Cross, James C.
Title The basic helix-loop-helix transcription factor Hand1 regulates mouse development as a homodimer
Journal name Developmental Biology   Check publisher's open access policy
ISSN 0012-1606
1095-564X
Publication date 2013-10-01
Sub-type Article (original research)
DOI 10.1016/j.ydbio.2013.07.025
Volume 382
Issue 2
Start page 470
End page 481
Total pages 12
Place of publication Maryland Heights, MO, United States
Publisher Academic Press
Language eng
Formatted abstract
Hand1 is a basic helix-loop-helix transcription factor that is essential for development of the placenta, yolk sac and heart during mouse development. While Hand1 is essential for trophoblast giant cell (TGC) differentiation, its potential heterodimer partners are not co-expressed in TGCs. To test the hypothesis that Hand1 functions as homodimer, we generated knock-in mice in which the Hand1 gene was altered to encode a tethered homodimer (TH). Some Hand1TH/− conceptuses in which the only form of Hand1 is Hand1TH are viable and fertile, indicating that homodimer Hand1 is sufficient for mouse survival. ~2/3 of Hand1TH/− and all Hand1TH/TH mice died in utero and displayed severe placental defects and variable cardial and cranial–facial abnormalities, indicating a dosage-dependent effect of Hand1TH. Meanwhile, expression of the Hand1TH protein did not have negative effects on viability or fertility in all Hand1TH/+ mice. These data imply that Hand1 homodimer plays a dominant role during development and its expression dosage is critical for survival, whereas Hand1 heterodimers can be either dispensable or play a regulatory role to modulate the activity of Hand1 homodimer in vivo.
Keyword Hand1
Basic helix-loop-helix
Transcription factor
Homodimer
Mouse development
Trophoblast
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Biomedical Sciences Publications
 
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