The Role of Fibroblast Growth Factor Receptor Substrate 2 (FRS2) in the Regulation of Two Activity Levels of the Components of the Extracellular Signal-Regulated Kinase (ERK) Pathway in the Mouse Epididymis1

Xu, Bingfang; Yang, Ling; Hinton, Barry T.

doi:10.1095/biolreprod.112.107185

Cited by 16 publications

(12 citation statements)

References 27 publications

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“… 49 50 51 52 53 54 Failure of IS epithelial cells to differentiate results in male infertility. 26 54 55 56 57 58 59 60 The IS epithelium receives luminal testicular factors from its junction with the efferent ducts. The establishment and maintenance of the IS epithelium require both androgen and lumicrine factors, 8 61 62 63 64 65 which include several hormones, ligands, and unknown factors that contribute to maintaining the MAPK pathway in an activated state in this segment 58 (Kim et al .…”

Section: Role Of Luminal Factors In the Maintenance And Remodeling Ofmentioning

confidence: 99%

Regulation of epithelial function, differentiation, and remodeling in the epididymis

et al. 2016

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The epididymis is a single convoluted tubule lined by a pseudostratified epithelium. Specialized epididymal epithelial cells, the so-called principal, basal, narrow, and clear cells, establish a unique luminal environment for the maturation and storage of spermatozoa. The epididymis is functionally and structurally divided into several segments and sub-segments that create regionally distinct luminal environments. This organ is immature at birth, and epithelial cells acquire their fully differentiated phenotype during an extended postnatal period, but the factors involved in this complex process remain incompletely characterized. In the adult epididymis, the establishment of an acidic luminal pH and low bicarbonate concentration in the epididymis contributes to preventing premature activation of spermatozoa during their maturation and storage. Clear cells are proton-secreting cells throughout the epididymis, but principal cells have distinct acid/base transport properties, depending on their localization within the epididymis. Basal cells are located in all epididymal segments, but they have a distinct morphology depending on the segment and species examined. How this structural plasticity of basal cells is regulated is discussed here. Also, the role of luminal factors and androgens in the regulation of epithelial cells is reviewed in relation to their respective localization in the proximal versus distal regions of the epididymis. Finally, we describe a novel role for CFTR in tubulogenesis and epithelial cell differentiation.

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Section: Role Of Luminal Factors In the Maintenance And Remodeling Ofmentioning

confidence: 99%

Regulation of epithelial function, differentiation, and remodeling in the epididymis

et al. 2016

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“…In the female reproductive tract, FGFs and FGFRs have been involved in folliculogenesis, embryo implantation and development [ 13 , 14 ]. Components of the FGF/FGFR pathway have also been found in tissues of the male reproductive tract from several species [ 6 , 15 , 16 ]. Transgenic mice expressing a dominant-negative variant of FGFR1 in the male haploid germ cells are subfertile, show diminished daily sperm output and reduced ability to undergo cellular changes associated with sperm capacitation [ 17 ], suggesting that this system has a relevant role in spermatogenesis/spermiogenesis and in the regulation of sperm physiology.…”

Section: Introductionmentioning

confidence: 99%

Fibroblast Growth Factor Receptors (FGFRs) in Human Sperm: Expression, Functionality and Involvement in Motility Regulation

et al. 2015

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Fibroblast growth factors receptors (FGFRs) have been widely characterized in somatic cells, but there is scarce evidence of their expression and function in mammalian gametes. The objective of the present study was to evaluate the expression of FGFRs in human male germ cells, to determine sperm FGFR activation by the FGF2 ligand and their participation in the regulation of sperm motility. The expression of FGFR1, 2, 3 and 4 mRNAs and proteins in human testis and localization of these receptors in germ cells of the seminiferous epithelium was demonstrated. In ejaculated sperm, FGFRs were localized to the acrosomal region and flagellum. Sperm exposure to FGF2 caused an increase in flagellar FGFR phosphorylation and activation of extracellular signal-regulated kinase (ERK) and protein kinase B (PKB or Akt) signaling pathways. Incubation with FGF2 led to a significant increase in the percentage of total and progressive sperm motility, as well as in sperm kinematics. All responses were prevented by sperm preincubation with BGJ398, a specific inhibitor of FGFR tyrosine kinase activity. In addition to confirming the expression of FGFRs in germ cells of the human testis, our study describes for the first time the presence, localization and functionality of human sperm FGFRs, and provides evidence of the beneficial effect of FGF2 upon sperm motility.

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“…1) Ptk7 was conditionally removed from epithelial cells in the most proximal regions of the epididymis from P17 onwards using Rnase10-Cre (Krutskikh et al, 2011) (Ptk7 flox/Xst87 :Rnase10-Cre tg , namely, RnCre-cKO); 2) Ptk7 was conditionally removed from epithelial cells in most epididymal regions except for the initial segment from embryonic stage onwards using Hoxb7-Cre (Yu et al, 2002) (Ptk7 flox/Xst87 :Hoxb7-Cre tg , namely, HoxCre-cKO; 3) Ptk7 was conditionally removed from smooth muscle cells from embryonic stage onwards using Sm22-Cre (Yoshida et al, 2010) (Ptk7 flox/Xst87 :Sm22-Cre tg , namely, SmCre-cKO). Recombination efficiency of Hoxb7-Cre and Rnase10-Cre in the Wolffian duct was examined previously (Xu et al, 2013). Recombination efficiency of SM22-Cre was tested in this study by breeding Cre mice with mT/mG Cre reporter mice.…”

Section: Resultsmentioning

confidence: 99%

Protein tyrosine kinase 7 is essential for tubular morphogenesis of the Wolffian duct

Washington

Domeniconi

et al. 2016

Developmental Biology

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The Wolffian duct, the proximal end of the mesonephric duct, undergoes non-branching morphogenesis to achieve an optimal length and size for sperm maturation. It is important to examine the mechanisms by which the developing mouse Wolffian duct elongates and coils for without proper morphogenesis, male infertility will result. Here we show that highly proliferative epithelial cells divide in a random orientation relative to the elongation axis in the developing Wolffian duct. Convergent extension (CE)-like of cell rearrangements is required for elongating the duct while maintaining a relatively unchanged duct diameter. The Wolffian duct epithelium is planar polarized, which is characterized by oriented cell elongation, oriented cell rearrangements, and polarized activity of regulatory light chain of myosin II. Conditional deletion of protein tyrosine kinase 7 (PTK7), a regulator of planar cell polarity (PCP), from mesoderm results in loss of the PCP characteristics in the Wolffian duct epithelium. Although loss of Ptk7 does not alter cell proliferation or division orientation, it affects CE and leads to the duct with significantly shortened length, increased diameter, and reduced coiling, which eventually results in loss of sperm motility, a key component of sperm maturation. In vitro experiments utilizing inhibitors of myosin II results in reduced elongation and coiling, similar to the phenotype of Ptk7 knockout. This data suggest that PTK7 signaling through myosin II regulates PCP, which in turn ensures CE-like of cell rearrangements to drive elongation and coiling of the Wolffian duct. Therefore, PTK7 is essential for Wolffian duct morphogenesis and male fertility.

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The Role of Fibroblast Growth Factor Receptor Substrate 2 (FRS2) in the Regulation of Two Activity Levels of the Components of the Extracellular Signal-Regulated Kinase (ERK) Pathway in the Mouse Epididymis1

Cited by 16 publications

References 27 publications

Regulation of epithelial function, differentiation, and remodeling in the epididymis

Regulation of epithelial function, differentiation, and remodeling in the epididymis

Fibroblast Growth Factor Receptors (FGFRs) in Human Sperm: Expression, Functionality and Involvement in Motility Regulation

Protein tyrosine kinase 7 is essential for tubular morphogenesis of the Wolffian duct

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