Female infertility in mice deficient in midkine and pleiotrophin, which form a distinct family of growth factors

Muramatsu, Hisako; Zou, Peng; Kurosawa, Nobuyuki; Ichihara-Tanaka, Keiko; Maruyama, Kiyoko; Inoh, Kazuhiko; Sakai, Takayuki; Chen, Lan; Muramatsu, Takashi

doi:10.1111/j.1365-2443.2006.01028.x

Cited by 83 publications

(84 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…An additional analysis has been conducted in the neural tube, where the scenario becomes more complicated owing to the partially overlapping expression patterns shown by Ptn and Mdk, which might be linked to functional redundancy (Mitsiadis et al, 1995). In fact, the severe phenotype associated with the double Ptn/Mdk mutation in mice, in contrast to mild phenotypes in the single mutants, has been explained on the basis of functional redundancy and compensation (Muramatsu et al, 2006). We have shown Ptnmediated Brd2 antagonism in three different systems: neuronal differentiation in P19 cells, neurogenesis in the neural tube and neural crest migration.…”

Section: Discussionmentioning

confidence: 93%

Pleiotrophin antagonizes Bromodomain-containing protein 2 (Brd2) during neuronal differentiation

García-Gutiérrez¹,

Juárez-Vicente²,

Wolgemuth³

et al. 2014

Journal of Cell Science

View full text Add to dashboard Cite

Bromodomain-containing protein 2 (Brd2) is a BET family chromatin adaptor required for expression of cell-cycle-associated genes and therefore involved in cell cycle progression. Brd2 is expressed in proliferating neuronal progenitors, displays cell-cycle-stimulating activity and, when overexpressed, impairs neuronal differentiation. Paradoxically, Brd2 is also detected in differentiating neurons. To shed light on the role of Brd2 in the transition from cell proliferation to differentiation, we had previously looked for proteins that interacted with Brd2 upon induction of neuronal differentiation. Surprisingly, we identified the growth factor pleiotrophin (Ptn). Here, we show that Ptn antagonized the cell-cycle-stimulating activity associated with Brd2, thus enhancing induced neuronal differentiation. Moreover, Ptn knockdown reduced neuronal differentiation. We analyzed Ptnmediated antagonism of Brd2 in a cell differentiation model and in two embryonic processes associated with the neural tube: spinal cord neurogenesis and neural crest migration. Finally, we investigated the mechanisms of Ptn-mediated antagonism and determined that Ptn destabilizes the association of Brd2 with chromatin. Thus, Ptnmediated Brd2 antagonism emerges as a modulation system accounting for the balance between cell proliferation and differentiation in the vertebrate nervous system.

show abstract

Section: Discussionmentioning

confidence: 93%

Pleiotrophin antagonizes Bromodomain-containing protein 2 (Brd2) during neuronal differentiation

García-Gutiérrez¹,

Juárez-Vicente²,

Wolgemuth³

et al. 2014

Journal of Cell Science

View full text Add to dashboard Cite

show abstract

“…All surgeries were performed under isoflurane anesthesia, and all efforts were made to minimize suffering. Ptprz-deficient mice (32) and Ptn-deficient mice (49) were back-crossed with the inbred C57BL/6 strain for over 10 generations.…”

Section: Methodsmentioning

confidence: 99%

Role of Chondroitin Sulfate (CS) Modification in the Regulation of Protein-tyrosine Phosphatase Receptor Type Z (PTPRZ) Activity

Kuboyama

Fujikawa

Suzuki

et al. 2016

Journal of Biological Chemistry

View full text Add to dashboard Cite

Protein-tyrosine phosphatase receptor type Z (PTPRZ) is predominantly expressed in the developing brain as a CS proteoglycan. PTPRZ has long (PTPRZ-A) and short type (PTPRZ-B) receptor forms by alternative splicing. The extracellular CS moiety of PTPRZ is required for high-affinity binding to inhibitory ligands, such as pleiotrophin (PTN), midkine, and interleukin-34; however, its functional significance in regulating PTPRZ activity remains obscure. We herein found that protein expression of CS-modified PTPRZ-A began earlier, peaking at approximately postnatal days 5-10 (P5-P10), and then that of PTN peaked at P10 at the developmental stage corresponding to myelination onset in the mouse brain. Ptn-deficient mice consistently showed a later onset of the expression of myelin basic protein, a major component of the myelin sheath, than wild-type mice. Upon ligand application, PTPRZ-A/B in cultured oligodendrocyte precursor cells exhibited punctate localization on the cell surface instead of diffuse distribution, causing the inactivation of PTPRZ and oligodendrocyte differentiation. The same effect was observed with the removal of CS chains with chondroitinase ABC but not polyclonal antibodies against the extracellular domain of PTPRZ. These results indicate that the negatively charged CS moiety prevents PTPRZ from spontaneously clustering and that the positively charged ligand PTN induces PTPRZ clustering, potentially by neutralizing electrostatic repulsion between CS chains. Taken altogether, these data indicate that PTN-PTPRZ-A signaling controls the timing of oligodendrocyte precursor cell differentiation in vivo, in which the CS moiety of PTPRZ receptors maintains them in a monomeric active state until its ligand binding.Myelination is an essential feature of the vertebrate nervous system that electrically insulates axons, thereby enabling the salutatory transmission of nerve impulses. Oligodendrocyte precursor cells (OPCs) 2 are the principal source of myelinating oligodendrocytes (1). Previous studies reported that protein tyrosine phosphorylation is crucially involved in the signal transduction mechanism for OPC differentiation into mature oligodendrocytes and myelin formation. FYN kinase in the Src tyrosine kinase family is the most prominent member involved in OPC differentiation and myelin formation (2). FYN activity is up-regulated during oligodendrocyte differentiation (3, 4), and Fyn-knock-out mice exhibit hypomyelination in the brain (5, 6). FYN phosphorylates p190 RhoGAP, a GTPase-activating protein (GAP) for Rho GTPase, to suppress Rho/ROCK, resulting in the maturation of oligodendrocytes and myelination (7,8).PTPRZ is the most abundant receptor-type protein-tyrosine phosphatase (RPTP) in OPCs (9, 10). PTPRZ dephosphorylates p190 RhoGAP, thereby acting as a counterpart of FYN (11,12). The amounts of myelin basic protein (MBP) and myelinated axons in the brain at postnatal day 10, when myelination occurs, are significantly higher in Ptprz-deficient mice than in wildtype animals, indicating a suppre...

show abstract

“…This study on PTN expression in mouse teeth serves as a model for the localization of PTN in human teeth. As it is difficult to carry out immunohistochemical studies in humans, a further and more detailed analysis that will involve the double knockout mouse (for both MK and PTN) (Muramatsu et al 2006) will be necessary to elucidate the exact involvement of the two-member family of redundant function growth factors PTN and MK during tooth formation and their regulation by BMPs. Pleiotrophin (PTN) antibody (Abcam; ab14025) dilutions were 1:50.…”

Section: Discussionmentioning

confidence: 99%

Pleiotrophin Expression during Odontogenesis

Erlandsen

Ames

Tamkenath

et al. 2012

J Histochem Cytochem.

View full text Add to dashboard Cite

SummaryPleiotrophin (PTN) is an extracellular matrix-associated growth factor and chemokine expressed in mesodermal and ectodermal cells. It plays an important role in osteoblast recruitment and differentiation. There is limited information currently available about PTN expression during odontoblast differentiation and tooth formation, and thus the authors aimed to establish the spatiotemporal expression pattern of PTN during mouse odontogenesis. Immortalized mouse dental pulp (MD10-D3, MD10-A11) and odontoblast-like (M06-G3) and ameloblast-like (EOE-3M) cell lines were grown and samples prepared for immunocytochemistry, Western blot, and conventional and quantitative PCR analysis. Effects of BMP2, BMP4, and BMP7 treatment on PTN expression in odontoblast-like M06-G3 cells were tested by quantitative PCR. Finally, immunohistochemistry of sectioned mice mandibles and maxillaries at developmental stages E16, E18, P1, P6, P10, and P28 was performed. The experiments showed that PTN, at both the mRNA and protein level, was expressed in all tested epithelial and mesenchymal dental cell lines and that the level of PTN mRNA was influenced differentially by the bone morphogenetic proteins. The authors observed initial expression of PTN in the inner enamel epithelium with prolonged expression in the ameloblasts and odontoblasts throughout their stages of maturation and strong expression in the terminally differentiated and enamel matrix-secreting ameloblasts and odontoblasts of the adult mouse incisors and molars. (J Histochem Cytochem 60:366-375, 2012)

show abstract

Female infertility in mice deficient in midkine and pleiotrophin, which form a distinct family of growth factors

Cited by 83 publications

References 41 publications

Pleiotrophin antagonizes Bromodomain-containing protein 2 (Brd2) during neuronal differentiation

Pleiotrophin antagonizes Bromodomain-containing protein 2 (Brd2) during neuronal differentiation

Role of Chondroitin Sulfate (CS) Modification in the Regulation of Protein-tyrosine Phosphatase Receptor Type Z (PTPRZ) Activity

Pleiotrophin Expression during Odontogenesis

Contact Info

Product

Resources

About