Homeobox gene Hex is essential for onset of mouse embryonic liver development and differentiation of the monocyte lineage.
Disruption of the mouse Hex gene resulted in embryonic lethality around embryonic age (E) 10.5, due to no substantial liver formation. Expression of albumin was detectable in heterozygous (Hex(+/-)) but not in homozygous (Hex(-/-)) [corrected] embryos at E8.5. Instead of liver bud formation at E9.5, a liver-like capsule structure was observed in Hex(-/-) [corrected] embryos. In Hex(-/-) [corrected] mutant liver, we found no hepatocytes but no signs of apoptotic cell death in the area. Expression of transcription factors involved in hepatocyte differentiation, hepatocyte nuclear factor (Hnf)3beta, Hnf6, Hnf4alpha and Hnf1alpha, were restricted to the capsule and internal matrix-like structure in the mutant liver and expression of a subset of these factors were reduced. Hematopoiesis of monocytes was impaired in mutant embryos while erythroid lineage was unaffected. These results indicate that Hex plays an essential role in progenitor cells which commit to the hepatic endoderm and in the hematopoietic differentiation of the monocyte lineage.
Keng
V W
VW
Graduate School of Bioagricultural Sciences, Chikusa-ku, Nagoya, 464-8601, Japan.
Yagi
H
H
Ikawa
M
M
Nagano
T
T
Myint
Z
Z
Yamada
K
K
Tanaka
T
T
Sato
A
A
Muramatsu
I
I
Okabe
M
M
Sato
M
M
Noguchi
T
T
D000418:Albumins / Q000235:genetics; D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D019070:Cell Lineage; D003114:Colony-Forming Units Assay; D004707:Endoderm / Q000166:cytology / Q000378:metabolism; D005313:Fetal Death; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D020043:Genes, Essential / Q000235:genetics; D005801:Genes, Homeobox / Q000235:genetics*; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology; D022781:Hepatocytes / Q000166:cytology; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D017403:In Situ Hybridization; D008099:Liver / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D051379:Mice; D009000:Monocytes / Q000166:cytology*; D009024:Morphogenesis; D009154:Mutation / Q000235:genetics; D009928:Organ Specificity; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism; D015017:Yolk Sac / Q000166:cytology / Q000378:metabolism
D000418:Albumins; C513080:Hhex protein, mouse; D018398:Homeodomain Proteins; D012333:RNA, Messenger; D014157:Transcription Factors