Patterns of keratins 8, 18 and 19 during gonadal differentiation in the mouse: sex- and time-dependent expression of keratin 19

Appert, Alexandre; Fridmacher, Valérie; Locquet, Odette; Magre, Solange

doi:10.1007/s002580050252

Cited by 8 publications

(12 citation statements)

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“…7A) (Pailhoux et al 2002, Sawyer et al 2002. Such an organization is not visible in the mouse ovary at the equivalent developmental stage (before 13·5 dpc) but occurs later, after 16·5 dpc (Appert et al 1998). According to these observations and to published data on the proliferative effect of estrogens and activin A at later stages of ovary development, one could envisage a similar role of these molecules on both somatic and germ cells during these early stages of ovarian development in the goat.…”

Section: Estrogens Are Decisive In Early Ovarian Development Across Vmentioning

confidence: 63%

FOXL2 activates P450 aromatase gene transcription: towards a better characterization of the early steps of mammalian ovarian development

Pannetier

Fabre²,

Batista³

et al. 2006

Journal of Molecular Endocrinology

231

173

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Previous studies have equated FOXL2 as a crucial actor in the ovarian differentiation process in different vertebrate species. Its transcriptional extinction in the polled intersex syndrome (PIS) leads primarily to a drastic decrease of aromatase (CYP19) expression in the first steps of goat ovarian development. In this study, we provide a better characterization of early ovarian development in goat, and we provide experimental evidence demonstrating that FOXL2 represents a direct transcriptional activator of the CYP19 gene through its ovarian-specific promoter 2. Moreover, the ovarian location of FOXL2 and CYP19 proteins, together with their expression profiles in the female gonads, stress the involvement of FOXL2 co-factor(s) for regulating CYP19 transcription. Expressional analyses show that activin-A can be considered as a strong candidate for being one of these FOXL2 co-factors. Finally, we discuss evidence for a role of activin and estrogens in somatic and germinal cell proliferation occurring before germ cell meiosis. This period, of 20 days in goat, seems to have no equivalent in mouse. This species-specific difference could explain the phenotype discrepancy observed between XX goat PIS −/− and XX mouse Foxl2 −/− .

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Section: Estrogens Are Decisive In Early Ovarian Development Across Vmentioning

confidence: 63%

FOXL2 activates P450 aromatase gene transcription: towards a better characterization of the early steps of mammalian ovarian development

Pannetier

Fabre²,

Batista³

et al. 2006

Journal of Molecular Endocrinology

231

173

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“…Since Atm function influences meiotic and mitotic telomere behavior and SECs usually display a few conspicuous telomere signals (telocenters) in tight association with their corresponding heterochromatin clusters (37,79), we also determined whether short-arm telomere distribution of the acrocentric mouse chromosomes and nuclear architecture is affected by the Atm mutation. We used vimentin IF to identify SECs and found, in contrast to wild-type mice, that the majority of mutant vimentin-positive SECs contained numerous heterochromatin clusters, a nuclear architecture usually observed in SECs of immature postnatal testes (16 (2,3). Besides SECs with immature heterochromatin distribution, the mutant testes also contained SECs with two heterochromatin clusters per nucleus, a feature frequently seen in normal adult mice.…”

Section: Discussionmentioning

confidence: 99%

“…Since elevated H1t IF signals could suggest skewed or immature differentiation of Atm-deficient SECs, we examined the expression of vimentin and cytokeratin 8 in the mutants and control. Vimentin is an intermediate filament marker expressed by SECs throughout development (3,24), while cytokeratin 8 expression marks lack of SEC differentiation, as it normally occurs only in fetal and early postnatal testes (2,66) and in SECs of infertile individuals or in association with testicular cancer (10,51,61). IF disclosed an increased frequency of vimentin-positive mutant SECs in relation to total testis cells (Table 2), which is most likely related to the absence of haploid cells and/or a response to the requirements for increased phagocytosis of the apoptotic bodies resulting from massive germ cell degeneration in the knockouts.…”

Section: Control C-ablmentioning

confidence: 99%

Meiotic Telomere Distribution and Sertoli Cell Nuclear Architecture Are Altered in Atm- andAtm-p53-Deficient Mice

Scherthan

Jerratsch

Dhar

et al. 2000

Molecular and Cellular Biology

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The ataxia telangiectasia mutant (ATM) protein is an intrinsic part of the cell cycle machinery that surveys genomic integrity and responses to genotoxic insult. Individuals with ataxia telangiectasia as well as Atm ؊/؊ mice are predisposed to cancer and are infertile due to spermatogenesis disruption during first meiotic prophase. Atm ؊/؊ spermatocytes frequently display aberrant synapsis and clustered telomeres (bouquet topology). Here, we used telomere fluorescent in situ hybridization and immunofluorescence (IF) staining of SCP3 and testes-specific histone H1 (H1t) to spermatocytes of Atm-and Atm-p53-deficient mice and investigated whether gonadal atrophy in Atm-null mice is associated with stalling of telomere motility in meiotic prophase. SCP3-H1t IF revealed that most Atm ؊/؊ p53 ؊/؊ spermatocytes degenerated during late zygotene, while a few progressed to pachytene and diplotene and some even beyond metaphase II, as indicated by the presence of a few round spermatids. In Atm ؊/؊ p53 ؊/؊ meiosis, the frequency of spermatocytes I with bouquet topology was elevated 72-fold. Bouquet spermatocytes with clustered telomeres were generally void of H1t signals, while mid-late pachytene and diplotene Atm ؊/؊ p53 ؊/؊ spermatocytes displayed expression of H1t and showed telomeres dispersed over the nuclear periphery. Thus, it appears that meiotic telomere movements occur independently of ATM signaling. Atm inactivation more likely leads to accumulation of spermatocytes I with bouquet topology by slowing progression through initial stages of first meiotic prophase and an ensuing arrest and demise of spermatocytes I. Sertoli cells (SECs), which contribute to faithful spermatogenesis, in the Atm mutants were found to frequently display numerous heterochromatin and telomere clusters-a nuclear topology which resembles that of immature SECs. However, Atm ؊/؊ SECs exhibited a mature vimentin and cytokeratin 8 intermediate filament expression signature. Upon IF with ATM antibodies, we observed ATM signals throughout the nuclei of human and mouse SECs, spermatocytes I, and haploid round spermatids. ATM but not H1t was absent from elongating spermatid nuclei. Thus, ATM appears to be removed from spermatid nuclei prior to the occurrence of DNA nicks which emanate as a consequence of nucleoprotamine formation.Ataxia telangiectasia is a rare human recessive autosomal disorder with a pleiotropic phenotype, specifically including progressive neurological degeneration, telangiectasia, often associated with premature aging, reduced size, immunodeficiency, sensitivity to ionizing radiation, cancer predisposition, and infertility (13,40,81,93). Mice mutated in the homologue of the ATM (ataxia telangiectasia mutated) gene (Atm) display similar pleiotropic defects (5, 27, 97). The ATM protein belongs to a growing family of phosphatidylinositol-3 kinaserelated kinases and seems to play a role as an intrinsic part of the cell cycle machinery that surveys genomic integrity, cell cycle progression, and processing of DNA damage. It shows sim...

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“…To identify gonadal structures, the distribution of specific markers was examined on sections adjacent to those treated for TIMP-1 analysis, using indirect immunofluorescence detection as described (Fridmacher et al, 1995;Appert et al, 1998). These markers are AMH/MIS for the identification of Sertoli cells (Josso et al, 1988), and fibronectin and keratin 8 for the identification of mesenchymal and epithelial cells (Appert et al, 1998), respectively.…”

Section: Histology and Immunohistochemistrymentioning

confidence: 99%

“…These markers are AMH/MIS for the identification of Sertoli cells (Josso et al, 1988), and fibronectin and keratin 8 for the identification of mesenchymal and epithelial cells (Appert et al, 1998), respectively. Antibodies used were a rabbit anti-AMH raised against bovine AMH (kindly provided by Dr. N. Josso), a rabbit antihuman plasma fibronectin serum (Life Technologies, Grand Island, NY, 6071 SA), and a monoclonal rat antikeratin 8 (TROMA-1, kindly provided by Dr R. Kemler).…”

Section: Histology and Immunohistochemistrymentioning

confidence: 99%

Differential expression of tissue inhibitor of metalloproteinases type 1 (TIMP‐1) during mouse gonad development

Guyot

Magre

Leduque

et al. 2003

Developmental Dynamics

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In mammals, the gene Sry initiates signaling pathways triggering the differentiation of a testis from a sexually indifferent gonad. Assuming that these morphogenetic events may alter the proteolytic balance, the expression of matrix metalloproteinases (MMPs) and inhibitors (TIMPs) was investigated in gonads from 11.5 days postcoitum (dpc) onward, when testicular organogenesis occurs. Whereas selective MMPs and TIMPs (1-3) were detected in undifferentiated gonads (11.5 dpc) and in neonatal testes, a single TIMP (TIMP-1) was expressed in a sexually dimorphic manner from 12.5 dpc onward (i.e., after overt male gonad differentiation), demonstrated by using a semiquantitative reverse transcriptase-polymerase chain reaction and a Western blot analysis. To gain insight into the role of TIMP-1, the expression of gelatinases (mRNA levels and enzyme activity) was monitored. However, no sex differences could be evidenced, indicating that TIMP-1 was not inhibiting this class of MMPs during testis organogenesis. Apart from being an inhibitor of MMPs, TIMP-1 is known to display growth promoting activities. Of interest, testicular TIMP-1 (but not TIMP-2) levels were further enhanced up to 2 weeks of age, consistent with a role in the early postnatal testicular growth. We, therefore, established an organotypic culture system in which seminiferous cords may differentiate de novo and grow, depending on culture conditions. In that system and mimicking the in vivo situation, TIMP-1 immunolocalized strongly within the male gonadal territory and weakly in female gonads, in which no organization was evident. Experiments are now under way to determine to what extent timp-1 is a morphogenic gene involved in seminiferous cord formation and development. Developmental Dynamics 227:357-366, 2003.

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Patterns of keratins 8, 18 and 19 during gonadal differentiation in the mouse: sex- and time-dependent expression of keratin 19

Cited by 8 publications

References 0 publications

FOXL2 activates P450 aromatase gene transcription: towards a better characterization of the early steps of mammalian ovarian development

FOXL2 activates P450 aromatase gene transcription: towards a better characterization of the early steps of mammalian ovarian development

Meiotic Telomere Distribution and Sertoli Cell Nuclear Architecture Are Altered in Atm- andAtm-p53-Deficient Mice

Differential expression of tissue inhibitor of metalloproteinases type 1 (TIMP‐1) during mouse gonad development

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