Villaescusa JC, et al reported the expression of Hox cofactor genes during mouse ovarian follicular development and oocyte maturation.
Very little is known about the expression and function of the HOX and HOX-cofactors genes in mammalian oogenesis. The aim of the present study was to determine the expression of PBX and PREP-1 gene products in the mouse ovary and their localization to particular ovarian compartment, specifically the oocyte-containing ovarian follicle. Immunocytochemical analysis demonstrated that PREP-1 was present in both granulosa cells and oocytes. PREP-1 was found in the nucleus in primary oocytes, but in the cytoplasm of fully-grown oocytes; in granulosa cells, however, PREP-1 was always localized to the nuclei. No PREP-1 immunoreactivity was found in corpus luteum, theca or stroma. PBX-1 was found in the cytosol of the oocyte, while PBX-2 expression was mostly restricted to the nuclei of granulosa cells. In addition, PBX-2 was also found in the nucleus of primary oocytes. Since PREP-PBX complexes act in vivo in conjunction with HOX transcription factors, we have used RT-PCR to identify HOX genes expressed in the ovary. This analysis identified transcripts for six HOX genes (A5, A9, B6, B7, C6 and C8) and two more TALE cofactors (PREP2 and Meis2). Thus, a number of HOX and HOX cofactor genes are expressed in the mammalian ovary. The restricted expression pattern for PBX-1 and PBX-2 and the changes in expression and localization of PREP-1 in the oocyte and granulosa cells suggest a previously unsuspected involvement of these transcription factors in oocyte maturation and development, as well as in granulosa cell differentiation.
NCBI Summary:
In vertebrates, the genes encoding the class of transcription factors called homeobox genes are found in clusters named A, B, C, and D on four separate chromosomes. Expression of these proteins is spatially and temporally regulated during embryonic development. This gene is part of the A cluster on chromosome 7 and encodes a DNA-binding transcription factor which may regulate gene expression, morphogenesis, and differentiation. Methylation of this gene may result in the loss of its expression and, since the encoded protein upregulates the tumor suppressor p53, this protein may play an important role in tumorigenesis.
General function
Nucleic acid binding, DNA binding, Transcription factor
Comment
Hoxa5/Cre transgenic mice: novel tools for regional deletion along the anterior-posterior axis. Brub-Simard FA 2013 et al.
The Hoxa5 homeobox gene encodes a transcription factor that plays a critical role in specifying the identity of the cervico-thoracic region along the anterior-posterior embryo axis and in orchestrating organ morphogenesis. The loss of Hoxa5 function results in skeletal transformations, lethality at birth due to lung defects, and organ anomalies affecting the digestive tract, the mammary gland and the ovary. Study of Hoxa5 gene regulation has revealed the interplay of several control regions that direct Hoxa5 developmental expression. Enhancers targeting expression in the CNS, the paraxial and lateral plate mesoderm at the cervico-thoracic level, and in the mesenchymal compartment of the respiratory and digestive tracts have been identified. Using these molecular tools, we have generated two Hoxa5/Cre transgenic mouse lines carrying different combinations of Hoxa5 regulatory enhancers and allowing site-specific recombination in subsets of Hoxa5 expression sites as tested with the Rosa26/lacZ reporter mice. Further validation of the recombination efficiency of the Hoxa5/Cre transgenic lines was performed with mice carrying a Hoxa5 conditional allele. Hoxa5 deletion with the Hoxa5/Cre mouse lines recapitulates Hoxa5 mutant phenotypes, such as skeletal defects, neonatal lethality and lung malformations. Hoxa5/Cre mouse lines provide novel genetic tools for gene function analysis in defined tissues along the anterior-posterior axis. 2013 Wiley Periodicals, Inc.
/////////////////////////
Cellular localization
Nuclear
Comment
Ovarian function
Oogenesis, Oocyte maturation
Comment
Expression regulated by
Comment
Ovarian localization
Comment
Follicle stages
Comment
Phenotypes
Mutations
1 mutations
Species: mouse
Mutation name: None
type: null mutation fertility: subfertile Comment: The Loss of Hoxa5 Function Causes Estrous Acyclicity and Ovarian Epithelial Inclusion Cysts. Gendronneau G et al. Hox genes encode transcription factors that play essential roles during embryo morphogenesis and organogenesis. Expression of several Hox members persists at the adult age, indicating a wide spectrum of action from embryonic to postnatal life. In the present study, we reported that in adult mice, the Hoxa5 gene shows a dynamic expression profile in the ovary that depends on the estrous cycle, the gestational status, and the age of the female, suggesting that Hoxa5 may have distinct physiological functions in the ovary. Consistent with a role for Hoxa5 in ovarian function, Hoxa5(-/-) nulliparous females exhibit precocious puberty and an early onset of estrous acyclicity. They show a prolonged estrous cycle with increased metestrus-diestrus length, a phenotype that worsens with age. Older mutant females also develop ovarian epithelial inclusion cysts reminiscent of human endosalpingiosis. Immunolabeling studies suggest that these cysts originate from the ovarian surface epithelium, a source of epithelial ovarian carcinomas. Staining of the Hoxa5(-/-) ovarian cysts by the ovarian cancer markers paired box gene 8 (PAX8) and Wilms' tumor 1 (WT1) further strengthens the notion that these cysts may constitute preneoplastic lesions. Moreover, the deregulation of the estrous cycle and the presence of ovarian epithelial cysts in Hoxa5(-/-) older females correlate with a reduced expression of specific epidermal growth factor receptor signaling components, namely Egfr, Areg, and Btc. Altogether, our data unveil that Hoxa5, a stroma-specific gene, plays a significant role in ovarian biology and may be involved in ovarian cancer predisposition.