DWnt-2, a Drosophila Wnt gene required for the development of the male reproductive tract, specifies a sexually dimorphic cell fate

Kozopas, Karen M.; Samos, Cindy Harryman; Nusse, Roel

doi:10.1101/gad.12.8.1155

Cited by 95 publications

(113 citation statements)

References 36 publications

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“…Wnt molecules play an important role in sexual determination and differentiation in species ranging from Drosophila to mice (30,31). Our results also showed that Wnt signaling is important for proper sexual differentiation in human males.…”

Section: Discussionsupporting

confidence: 60%

Synergistic Cooperation between the β-Catenin Signaling Pathway and Steroidogenic Factor 1 in the Activation of the Mullerian Inhibiting Substance Type II Receptor

Hossain

Saunders

2003

Journal of Biological Chemistry

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Mullerian inhibiting substance type II receptor (MISRII) is a member of the transforming growth factor-␤ superfamily. Mutations in mullerian inhibiting substance (MIS) or MISRII cause male sexual abnormalities, persistent mullerian duct syndrome, and pseudohermaphroditism. The spatial and temporal regulation of MIS and MISRII is important for its biological action. Male Wnt7a mutant mice do not undergo regression of mullerian ducts. Here we showed that the canonical Wnt signaling pathway regulated MISRII. The promoter MISRII was activated by ␤-catenin expression, and this activation was dependent on TCF4-binding sites. The nuclear receptor superfamily member steroidogenic factor 1 (SF1) synergistically activated the MISRII promoter with ␤-catenin. APC, a negative regulator of Wnt signaling, decreased SF1-mediated activation of the MISRII promoter in the colon carcinoma cell line SW480. We also showed a direct physical interaction between ␤-catenin and SF1 by co-immunoprecipitation. Thus, our findings suggest that MISRII is a developmental target of Wnt7a signaling for mullerian duct regression during sexual differentiation.

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Section: Discussionsupporting

confidence: 60%

Synergistic Cooperation between the β-Catenin Signaling Pathway and Steroidogenic Factor 1 in the Activation of the Mullerian Inhibiting Substance Type II Receptor

Hossain

Saunders

2003

Journal of Biological Chemistry

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“…Of the Drosophila Wnts, only DWnt2 is expressed in the posterior gut primordium at the appropriate time. However, £ies homozygous for a null allele of DWnt2 are viable (Kozopas et al 1998), suggesting either that Dwnt2 is not active in specifying tubule cells or that a maternal contribution of Dwnt2 provides the ligand. Further work is required to assess the role of Dwnt2 and if necessary, to search for other members of the Wnt family, as the full sequence of the £y genome becomes available.…”

Section: The Allocation Of Malpighian Tubule Cells and The Formation mentioning

confidence: 99%

Coordinating cell fate and morphogenesis inDrosophilarenal tubules

Ainsworth

Wan

Skaer

2000

Phil. Trans. R. Soc. Lond. B

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Using the renal tubules of Drosophila as an example, we explore how cell speci¢cation leads to the morphogenetic movements that underlie the generation of tissue architecture. Taking two stages of development, we show ¢rst that the tubule cells are allocated by signalling between the endodermal and ectodermal compartments of the posterior gut. Activation of the Wnt pathway patterns the ectodermal anlage, resulting in the expression of tubule genes in a subset of cells and their eversion from the hindgut to form the tubule primordia. We argue that early gene expression directs these morphogenetic movements but not the complete programme of tubule di¡erentiation. In the second example we show that the allocation of the mitogenic tip cell lineage in each tubule is required not only for the normal pattern of cell division but also for the stereotyped three-dimensional arrangement of the mature tubules. Analysis of mutants in which the tip cell lineage is misspeci¢ed reveals that both daughters of the tip cell progenitor are required for the tubules to navigate through the body cavity, so that the distal tips locate in their characteristic positions. We show that the regulator of Rac, Myoblast city, is essential for this second morphogenetic process.

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“…In Drosophila, disruption of Dwnt-2 gene causes loss of the male-specific pigment cells in the reproductive tract sheath (37), indicating that Wnt signaling carries crucial functions in testicular development. During mouse spermiogenesis, the round spermatids proceed to an elongation phase in which they are sculptured into the shape of mature spermatozoa (38).…”

Section: Role Of Nkd1 In Mouse Embryonicmentioning

confidence: 99%

A Targeted Mutation of Nkd1 Impairs Mouse Spermatogenesis

Ishikawa

Miyoshi

et al. 2005

Journal of Biological Chemistry

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Nkd1 is an antagonist of the canonical Wnt/␤-catenin signaling pathway. The EF-hand motif of Nkd1 is required for its inhibitory function. Early studies suggested that Nkd1 might play important roles in mouse embryonic development and tumorigenesis. We constructed Nkd1 ؊/؊ mice whose Nkd1 protein lacked the EF-hand and was unable to inhibit Wnt/␤-catenin signaling. The homozygotes were viable and grew normally, but their fertility in males was reduced. In wild-type adult testes, Nkd1 mRNA was expressed more abundantly in the elongating spermatids than in the round spermatids. Lack of EF-hand caused reductions in the testis weight and sperm count by 30 and 60%, respectively. During testis development, Nkd1 mRNA expression started at the 25th day after birth, coincident with the onset of Wnt1 expression. Nuclear localization of ␤-catenin increased in the elongating spermatids, suggesting that the mutant Nkd1 failed to inhibit the Wnt/ ␤-catenin pathway. These results suggest that deletion of the EF-hand from Nkd1 reduces the number of the elongating spermatids at haploid stage. In contrast, the mutant Nkd1 did not affect intestinal polyposis in Apc ⌬716 mice.

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DWnt-2, a Drosophila Wnt gene required for the development of the male reproductive tract, specifies a sexually dimorphic cell fate

Cited by 95 publications

References 36 publications

Synergistic Cooperation between the β-Catenin Signaling Pathway and Steroidogenic Factor 1 in the Activation of the Mullerian Inhibiting Substance Type II Receptor

Synergistic Cooperation between the β-Catenin Signaling Pathway and Steroidogenic Factor 1 in the Activation of the Mullerian Inhibiting Substance Type II Receptor

Coordinating cell fate and morphogenesis inDrosophilarenal tubules

A Targeted Mutation of Nkd1 Impairs Mouse Spermatogenesis

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