Sexually dimorphic expression of protease nexin-1 and vanin-1 in the developing mouse gonad prior to overt differentiation suggests a role in mammalian sexual development

Grimmond, Sean M.; Hateren, Nick Van; Siggers, Pam; Arkell, Ruth M.; Larder, Rachel; Soares, Marcelo B.; Bonaldo, Maria de Fátima; Smith, Lee B.; Tymowska-Lalanne, Zuzanna; Wells, Christine A.; Greenfield, Andy

doi:10.1093/hmg/9.10.1553

Cited by 95 publications

(64 citation statements)

References 40 publications

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“…Microarrays were constructed by using randomly picked polymerase chain reaction (PCR)-amplified cDNA clones from the developing urogenital ridge library NMUR (Grimmond et al, 2000). To overcome the limitations imposed by the small amounts of RNA available from embryonic tissue, a Taq polymerasebased amplification procedure was used before labeling of RNA (see Experimental Procedures section and Smith et al, 2003).…”

Section: Resultsmentioning

confidence: 99%

“…A normalized cDNA library (NMUR) from urogenital ridges (UGRs) dissected from 11.5 and 12.5 dpc embryos was used as a source of cDNA clones for microarray construction, as previously described (Grimmond et al, 2000). Total RNA was prepared from embryonic gonads at 13.5 dpc as previously described (Grimmond et al, 2000).…”

Section: Dna Microarray Analysismentioning

confidence: 99%

“…The putative missing genes from this pathway, such as those encoding additional membrane-bound or secreted signaling molecules, their receptors, signal transduction elements, protein trafficking mediators, nuclear import/ export regulators, growth factors, enzymes, and structural proteins remain to be identified. We have described recently a DNA microarraybased screen for genes exhibiting sexually dimorphic transcription during mouse gonad development that identified the molecules Vanin-1 and Pn-1 as potential elements in sexual development (Grimmond et al, 2000). By using the same strategy, we describe here the identification of a novel gene, Maestro (Mro), which exhibits male-specific transcription both before and after overt differentiation of the testis.…”

Section: Introductionmentioning

confidence: 99%

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Candidate testis‐determining gene, Maestro (Mro), encodes a novel HEAT repeat protein

Smith

Hateren

Willan

et al. 2003

Developmental Dynamics

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Mammalian sex determination depends on the presence or absence of SRY transcripts in the embryonic gonad. Expression of SRY initiates a pathway of gene expression resulting in testis development. Here, we describe a novel gene potentially functioning in this pathway using a cDNA microarray screen for genes exhibiting sexually dimorphic expression during murine gonad development. Maestro (Mro) transcripts are first detected in the developing male gonad before overt testis differentiation. By 12.5 days postcoitus (dpc), Mro transcription is restricted to the developing testis cords and its expression is not germ cell-dependent. No expression is observed in female gonads between 10.5 and 14.5 dpc. Maestro encodes a protein containing HEAT-like repeats that localizes to the nucleolus in cell transfection assays. Maestro maps to a region of mouse chromosome 18 containing a genetic modifier of XX sex reversal. We discuss the possible function of Maestro in light of these data. Developmental Dynamics 227: 600 -607, 2003.

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Section: Resultsmentioning

confidence: 99%

Section: Dna Microarray Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Candidate testis‐determining gene, Maestro (Mro), encodes a novel HEAT repeat protein

Smith

Hateren

Willan

et al. 2003

Developmental Dynamics

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“…Recently, several large scale transcriptome experiments have been performed to study genital ridge gene expression. Several laboratories have employed subtractive screens or microarray analysis to search for sexually dimorphic gene expression between male and female whole embryonic mouse gonads (Bowles et al, 2000a;Grimmond et al, 2000;Wertz and Herrmann, 2000;Menke and Page, 2002;McClive et al, 2003;Smith et al, 2003;Small et al, 2005). More recently, transgenic mouse models expressing fluorescent proteins driven by various lengths of SRY or Sf1 promoters have been developed and used to compare gene expression of specific cell types within the genital ridge around the time of sex determination and differentiation (Boyer et al, 2004;Nef et al, 2005;Beverdam and Koopman, 2006;Bouma et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Presumptive pre‐sertoli cells express genes involved in cell proliferation and cell signalling during a critical window in early testis differentiation

Cory

Boyer

Pilon

et al. 2007

Molecular Reproduction Devel

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In mammals, the pre-Sertoli cell of the male genital ridge is the first cell type to display sex specific differentiation and differential gene expression. The genetic cascade driving the differentiationof pre-Sertoli cells and ultimately testis formationis beginning to be unravelled, but many questions remain. A better understanding of the transcriptome of pre-Sertoli cells immediately after sex determination is essential in order to further understand this differentiationprocess. A mouse model expressing Red Fluorescent Protein (RFP) under the control of a hybrid mouse/pig SRY promoter (HybSRYp-RFP) was used to purify cells from embryonic day 12.0 (e12.0) male genital ridges. To compare the transcriptomes of HybSRYp-RFP cell populations versus age matched whole female genital ridges, RNA was extracted and used to generate molecular probes that were hybridized onto Affymetrix Mouse Genome 430 2.0 microarrays. The expression of genes considered markers for pre-Sertoli cells, including Sox9, Mis, Dhh and Fgf9 were identified within the HybSRYp-RFP expressing cell population, while markers for germ cells (Oct4, SSEA-1) and endothelial cells (Ntrk3) were not identified. In contrast, markers for ovarian somatic cell expression, including Fst and Bmp2, were identified as overexpressed within the ovarian cell population. In a general fashion, genes identified as 2.5-fold over expressed in HybSRYp-RFP expressing cells coded notably for cell signalling and extra cellular proteins. The expression of Sox10, Stc2, Fgf18, Fgf13 and Wnt6 were further characterized via whole mount in situ hybridization (WISH) on male and female genital ridges between e11.5 and e14.5. Sox10, Fgf18, Fgf13 and Stc2 gene expression was detected within the male genital ridges while Wnt6 was found diffusely within both the male and female genital ridges. These data represent the earliest comprehensive microarray expression analysis of purified presumptive pre-Sertoli cells available to date. Mol. Reprod. Dev. 74: 1491-1504, 2007

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“…Other inhibitors of proteinases have been shown previously to display a sexually dimorphic pattern of expression and may contribute to the proteolytic equilibrium. These include testatin, a cystatin-related gene (Tö hö nen et al, 1998, Kanno et al, 1999, and protease nexin-1 (Grimmond et al, 2000), a serineprotease inhibitor. Whether TIMP-3 should also be added to this growing list of genes likely to intervene in tissue reorganization during early testis development remains controversial.…”

Section: Timp-1 Exhibits a Sex-dimorphic Pattern Of Expressionmentioning

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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Sexually dimorphic expression of protease nexin-1 and vanin-1 in the developing mouse gonad prior to overt differentiation suggests a role in mammalian sexual development

Cited by 95 publications

References 40 publications

Candidate testis‐determining gene, Maestro (Mro), encodes a novel HEAT repeat protein

Candidate testis‐determining gene, Maestro (Mro), encodes a novel HEAT repeat protein

Presumptive pre‐sertoli cells express genes involved in cell proliferation and cell signalling during a critical window in early testis differentiation

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

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