Hoxa-10 Deficiency Alters Region-specific Gene Expression and Perturbs Differentiation of Natural Killer Cells During Decidualization.
From: Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Developmental biology
- Publish Date: Feb 2006
- ISSN: 0012-1606
- Volume: 290
- Issue: 1
- Pages: 105-17
- Medium: Print
- Language: English
- Citation (JAMA): Rahman Mohammad A, Li Meiling, Li Ping, et al. Hoxa-10 Deficiency Alters Region-specific Gene Expression and Perturbs Differentiation of Natural Killer Cells During Decidualization.. Dev. Biol. Feb 2006;290:105-17
Abstract
Uterine decidualization, a key event for successful implantation, is critically controlled by stromal cell proliferation and differentiation. One hallmark event of decidualization is the acquisition of stromal cell polyploidy through terminal differentiation at the anti-mesometrial pole of the implantation site. Hoxa-10, a developmentally regulated homeobox transcription factor, is highly expressed in decidualizing stromal cells, and targeted deletion of Hoxa-10 in mice shows severe decidualization defects, primarily due to reduced stromal cell responsiveness to progesterone. However, the underlying molecular mechanism by which Hoxa-10 regulates this process remains largely unknown. Here, we show that Hoxa-10 deficiency confers diminished core cell cycle activity during stromal cell proliferation without disturbing polyploidy, suggesting that these events depend on local regulators that impact cell cycle machinery. To further address this question, we compared global gene expression profiles in uteri of wild-type and Hoxa-10(-/-) mice after inducing decidualization. Our studies show two major aspects of decidualization downstream of Hoxa-10. First, Hoxa-10 deficiency results in the aberrant region-specific expression of cyclin-dependent kinase-4 (cdk4) and -6 (cdk6), growth differentiation factor 10 (Gdf10), hepatocyte growth factor (Hgf) and Snail2. Second, Hoxa-10 deficiency compromises natural killer (NK) cell differentiation without altering trafficking of NK precursor cells during decidualization. Collectively, the results provide evidence that Hoxa-10 influences a host of genes and cell functions necessary for propagating normal decidual development during the post-implantation period.
Mesh Headings (Keywords): Animals, Bone Morphogenetic Proteins, Cell Cycle, Cell Differentiation, Cell Proliferation, Cyclin-Dependent Kinase 4, Cyclin-Dependent Kinase 6, Decidua, Embryo Implantation, Female, Gene Expression Regulation, Developmental, Hepatocyte Growth Factor, Homeodomain Proteins, Killer Cells, Natural, Mice, Mice, Knockout, Oligonucleotide Array Sequence Analysis, Polyploidy, Signal Transduction, Transcription Factors, Uterus
Check for Full Text / PubMed Unique Identifier (PMID): 16337623
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.