Functional ablation of the mouse Ldb1 gene results in severe patterning defects during gastrulation.
The LIM domain-binding protein 1 (Ldb1) is found in multi-protein complexes containing various combinations of LIM-homeodomain, LIM-only, bHLH, GATA and Otx transcription factors. These proteins exert key functions during embryogenesis. Here we show that targeted deletion of the Ldb1 gene in mice results in a pleiotropic phenotype. There is no heart anlage and head structures are truncated anterior to the hindbrain. In about 40% of the mutants, posterior axis duplication is observed. There are also severe defects in mesoderm-derived extraembryonic structures, including the allantois, blood islands of the yolk sack, primordial germ cells and the amnion. Abnormal organizer gene expression during gastrulation may account for the observed axis defects in Ldb1 mutant embryos. The expression of several Wnt inhibitors is curtailed in the mutant, suggesting that Wnt pathways may be involved in axial patterning regulated by Ldb1.
Mukhopadhyay
Mahua
M
Department of Anatomy, University of Wisconsin-Madison Medical School, Madison, WI 53706, USA.
Teufel
Andreas
A
Yamashita
Tsuyoshi
T
Agulnick
Alan D
AD
Chen
Lan
L
Downs
Karen M
KM
Schindler
Alice
A
Grinberg
Alexander
A
Huang
Sing-Ping
SP
Dorward
David
D
Westphal
Heiner
H
D000818:Animals; D001483:Base Sequence; D019521:Body Patterning / Q000235:genetics* / Q000502:physiology; D004247:DNA / Q000235:genetics; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D005260:Female; D005318:Fetal Heart / Q000196:embryology; D005775:Gastrula / Q000166:cytology* / Q000378:metabolism; D018390:Gene Targeting; D060588:LIM Domain Proteins; D008297:Male; D008648:Mesoderm / Q000166:cytology; D051379:Mice; D018345:Mice, Knockout; D009865:Oocytes / Q000378:metabolism; D010641:Phenotype; D011247:Pregnancy; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051153:Wnt Proteins; D029961:Zebrafish Proteins
D004268:DNA-Binding Proteins; D060588:LIM Domain Proteins; C102084:Ldb1 protein, mouse; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D051153:Wnt Proteins; D029961:Zebrafish Proteins; C486313:ldb1a protein, zebrafish; D004247:DNA