TY - JOUR
T1 - The AML1 transcription factor functions to develop and maintain hematogenic precursor cells in the embryonic aorta-gonad-mesonephros region
AU - Mukouyama, Yoh suke
AU - Chiba, Natsuko
AU - Hara, Takahiko
AU - Okada, Hitoshi
AU - Ito, Yoshiaki
AU - Kanamaru, Ryunosuke
AU - Miyajima, Atsushi
AU - Satake, Masanobu
AU - Watanabe, Toshio
N1 - Funding Information:
We thank I. Imamura for her secretarial work. Y.M. is supported by Research Fellowships of the Japan Society for the Promotion of Science for Young Scientists. This investigation was supported by research grants from the Ministry of Education, Science, Sports, and Culture of Japan.
PY - 2000/4/1
Y1 - 2000/4/1
N2 - We examined the role of the AML1 transcription factor in the development of hematopoiesis in the paraaortic splanchnopleural (P-Sp) and the aorta- gonad-mesonephros (AGM) regions of mouse embryos. The activity of colony- forming units of colonies from the P-Sp/AGM region was reduced severalfold by heterozygous disruption of the AML1 gene, indicating that AML1 functioned in a dosage-dependent manner to generate hematopoietic progenitors. In addition, no hematopoietic progenitor activity was detected in the P-Sp/AGM region of embryos with an AML1 null mutation. Similar results were obtained when a dispersed culture was first prepared from the P-Sp/AGM region before assay of the activity of the colony-forming units. In a culture of cells with the AML1(+/+) genotype, both hematopoietic and endothelial-like cell types emerged, but in a culture of cells with the AML1(-/-) genotype, only endothelial-like cells emerged. Interestingly, introduction of AML1 cDNA into the P-Sp/AGM culture with the AML1(-/-) genotype partially restored the production of hematopoietic cells. This restoration was observed for cultures prepared from 9.5-day postcoitum (dpc) embryos but not for cultures prepared from 11.5-dpc embryos. Therefore, the population of endothelial-like cells capable of growing in the AML1(-/-) culture would appear to contain inert but nonetheless competent hematogenic precursor cells up until at least the 9.5- dpc period. All these results support the notion that the AML1 transcription factor functions to develop and maintain hematogenic precursor cells in the embryonic P-Sp/AGM region. (C) 2000 Academic Press.
AB - We examined the role of the AML1 transcription factor in the development of hematopoiesis in the paraaortic splanchnopleural (P-Sp) and the aorta- gonad-mesonephros (AGM) regions of mouse embryos. The activity of colony- forming units of colonies from the P-Sp/AGM region was reduced severalfold by heterozygous disruption of the AML1 gene, indicating that AML1 functioned in a dosage-dependent manner to generate hematopoietic progenitors. In addition, no hematopoietic progenitor activity was detected in the P-Sp/AGM region of embryos with an AML1 null mutation. Similar results were obtained when a dispersed culture was first prepared from the P-Sp/AGM region before assay of the activity of the colony-forming units. In a culture of cells with the AML1(+/+) genotype, both hematopoietic and endothelial-like cell types emerged, but in a culture of cells with the AML1(-/-) genotype, only endothelial-like cells emerged. Interestingly, introduction of AML1 cDNA into the P-Sp/AGM culture with the AML1(-/-) genotype partially restored the production of hematopoietic cells. This restoration was observed for cultures prepared from 9.5-day postcoitum (dpc) embryos but not for cultures prepared from 11.5-dpc embryos. Therefore, the population of endothelial-like cells capable of growing in the AML1(-/-) culture would appear to contain inert but nonetheless competent hematogenic precursor cells up until at least the 9.5- dpc period. All these results support the notion that the AML1 transcription factor functions to develop and maintain hematogenic precursor cells in the embryonic P-Sp/AGM region. (C) 2000 Academic Press.
KW - AGM region
KW - AML1
KW - Gene targeting
KW - Hematopoietic development
KW - Transcription factor
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U2 - 10.1006/dbio.2000.9617
DO - 10.1006/dbio.2000.9617
M3 - Article
C2 - 10720428
AN - SCOPUS:0034176176
VL - 220
SP - 27
EP - 36
JO - Developmental Biology
JF - Developmental Biology
SN - 0012-1606
IS - 1
ER -