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Articles 1 - 25 of 25
Full-Text Articles in Life Sciences
Nell2 Regulates The Contralateral-Versus-Ipsilateral Visual Projection As A Domain-Specific Positional Cue, Chizu Nakamoto, Elaine Durward, Masato Horie, Masaru Nakamoto
Nell2 Regulates The Contralateral-Versus-Ipsilateral Visual Projection As A Domain-Specific Positional Cue, Chizu Nakamoto, Elaine Durward, Masato Horie, Masaru Nakamoto
Biology Faculty Publications
In mammals with binocular vision, retinal ganglion cell (RGC) axons from each eye project to eye-specific domains in the contralateral and ipsilateral dorsal lateral geniculate nucleus (dLGN), underpinning disparity-based stereopsis. Although domain-specific axon guidance cues that discriminate contralateral and ipsilateral RGC axons have long been postulated as a key mechanism for development of the eye-specific retinogeniculate projection, the molecular nature of such cues has remained elusive. Here, we show that the extracellular glycoprotein Nell2 (neural epidermal growth factor-like-like 2) is expressed in the dorsomedial region of the dLGN, which ipsilateral RGC axons terminate in and contralateral axons avoid. In Nell2 …
The Developmental And Genetic Basis Of ‘Clubfoot’ In The Peroneal Muscular Atrophy Mutant Mouse, J. Martin Collinson, Nils Lindström, Carlos Neves, Karen Wallace, Caroline Meharg, Rebecca Charles, Zoe Ross, Amy Fraser, Ivan Mbogo, Kadri Oras, Masaru Nakamoto, Simon Barker, Suzanne Duce, Zosia Miedzybrodzka, Neil Vargesson
The Developmental And Genetic Basis Of ‘Clubfoot’ In The Peroneal Muscular Atrophy Mutant Mouse, J. Martin Collinson, Nils Lindström, Carlos Neves, Karen Wallace, Caroline Meharg, Rebecca Charles, Zoe Ross, Amy Fraser, Ivan Mbogo, Kadri Oras, Masaru Nakamoto, Simon Barker, Suzanne Duce, Zosia Miedzybrodzka, Neil Vargesson
Biology Faculty Publications
Genetic factors underlying the human limb abnormality congenital talipes equinovarus (‘clubfoot’) remain incompletely understood. The spontaneous autosomal recessive mouse ‘peroneal muscular atrophy’ mutant (PMA) is a faithful morphological model of human clubfoot. In PMA mice, the dorsal (peroneal) branches of the sciatic nerves are absent. In this study, the primary developmental defect was identified as a reduced growth of sciatic nerve lateral motor column (LMC) neurons leading to failure to project to dorsal (peroneal) lower limb muscle blocks. The pma mutation was mapped and a candidate gene encoding LIM-domain kinase 1 (Limk1) identified, which is upregulated in mutant lateral LMC …
Transposon-Mediated Stable Suppression Of Gene Expression In The Developing Chick Retina, Masaru Nakamoto, Chizu Nakamoto
Transposon-Mediated Stable Suppression Of Gene Expression In The Developing Chick Retina, Masaru Nakamoto, Chizu Nakamoto
Biology Faculty Publications
The embryonic chick has long been a favorite model system for in vivo studies of vertebrate development. However, a major technical limitation of the chick embryo has been the lack of efficient loss-of-function approaches for analyses of gene functions. Here, we describe a methodology in which a transgene encoding artificial microRNA sequences is introduced into embryonic chick retinal cells by in ovo electroporation and integrated into the genome using the Tol2 transposon system. We show that this methodology can induce potent and stable suppression of gene expression. This technique therefore provides a rapid and robust loss-of-function approach for studies of …
Doing It Again: Repeating Methodology From Published Literature To Learn Field Biology, Laurie Eberhardt
Doing It Again: Repeating Methodology From Published Literature To Learn Field Biology, Laurie Eberhardt
Biology Faculty Publications
Repeatability underpins a basic assumption in science which students must learn in order to evaluate others’ research findings as well as to communicate the results of their own research. By attempting to repeat the methods of published studies, students learn the importance of clear written communication, while at the same time developing research skills. I describe three examples of published field studies that can be used as the basis for course exercises on the repeatability of methodology, as well as field sampling techniques, all grounded in the overall topic of environmental change. Two of the exercises returned students to the …
Expression And Regulatory Effects On Cancer Cell Behavior Of Nell1 And Nell2 In Human Renal Cell Carcinoma, Ritsuko Nakamura, Takeru Oyama, Ryosuke Tajiri, Atsushi Mizokami, Mikiko Namiki, Masaru Nakamoto, Akishi Ooi
Expression And Regulatory Effects On Cancer Cell Behavior Of Nell1 And Nell2 In Human Renal Cell Carcinoma, Ritsuko Nakamura, Takeru Oyama, Ryosuke Tajiri, Atsushi Mizokami, Mikiko Namiki, Masaru Nakamoto, Akishi Ooi
Biology Faculty Publications
Neural epidermal growth factor-like like (NELL) 1 and 2 constitute a family of multimeric and multimodular extracellular glycoproteins. Although the osteogenic effects of NELL1 and functions of NELL2 in neural development have been reported, their expression and functions in cancer are largely unknown. In this study, we examined expression of NELL1 and NELL2 in renal cell carcinoma (RCC) using clinical specimens and cell lines. We show that, whereas NELL1 and NELL2 proteins are strongly expressed in renal tubules in non-cancerous areas of RCC specimens, their expression is significantly downregulated in cancerous areas. Silencing of NELL1 and NELL2 mRNA expression was …
Nel Positively Regulates The Genesis Of Retinal Ganglion Cells By Promoting Their Differentiation And Survival During Development, Chizu Nakamoto, Soh-Leh Kuan, Amy Findlay, Elaine Durward, Zhufeng Ouyang, Masaru Nakamoto, Ewa Zakrewska, Takuma Endo
Nel Positively Regulates The Genesis Of Retinal Ganglion Cells By Promoting Their Differentiation And Survival During Development, Chizu Nakamoto, Soh-Leh Kuan, Amy Findlay, Elaine Durward, Zhufeng Ouyang, Masaru Nakamoto, Ewa Zakrewska, Takuma Endo
Biology Faculty Publications
For correct functioning of the nervous system, the appropriate number and complement of neuronal cell types must be produced during development. However, the molecular mechanisms that regulate the production of individual classes of neurons are poorly understood. In this study, we investigate the function of the thrombospondin-1–like glycoprotein, Nel (neural epidermal growth factor [EGF]-like), in the generation of retinal ganglion cells (RGCs) in chicks. During eye development, Nel is strongly expressed in the presumptive retinal pigment epithelium and RGCs. Nel overexpression in the developing retina by in ovo electroporation increases the number of RGCs, whereas the number of displaced amacrine …
Structure-Function Analysis Of Nel, A Thrombospondin-1-Like Glycoprotein Involved In Neural Development And Functions, Masaru Nakamoto
Structure-Function Analysis Of Nel, A Thrombospondin-1-Like Glycoprotein Involved In Neural Development And Functions, Masaru Nakamoto
Biology Faculty Publications
Nel (neural epidermal growth factor (EGF)-like molecule) is a multimeric, multimodular extracellular glycoprotein with heparin-binding activity and structural similarities to thrombospondin-1. Nel is predominantly expressed in the nervous system and has been implicated in neuronal proliferation and differentiation, retinal axon guidance, synaptic functions, and spatial learning. The Nel protein contains an N-terminal thrombospondin-1 (TSP-N) domain, five cysteine-rich domains, and six EGF-like domains. However, little is known about the functions of specific domains of the Nel protein. In this study, we have performed structure-function analysis of Nel, by using a series of expression constructs for different regions of the Nel protein. …
Cyp704b1 Is A Long-Chain Fatty Acid V-Hydroxylase Essential For Sporopollenin Synthesis In Pollen Of Arabidopsis, Anna A. Dobritsa, Jay Shrestha, Marc Morant, Franck Pinot, Michiyo Matsuno, Rob Swanson, Birger Lindberg Møller, Daphne Preuss
Cyp704b1 Is A Long-Chain Fatty Acid V-Hydroxylase Essential For Sporopollenin Synthesis In Pollen Of Arabidopsis, Anna A. Dobritsa, Jay Shrestha, Marc Morant, Franck Pinot, Michiyo Matsuno, Rob Swanson, Birger Lindberg Møller, Daphne Preuss
Biology Faculty Publications
Sporopollenin is the major component of the outer pollen wall (exine). Fatty acid derivatives and phenolics are thought to be itsmonomeric building blocks, but the precise structure, biosynthetic route, and genetics of sporopollenin are poorly understood.Based on a phenotypic mutant screen in Arabidopsis (Arabidopsis thaliana), we identified a cytochrome P450, designatedCYP704B1, as being essential for exine development. CYP704B1 is expressed in the developing anthers. Mutations in CYP704B1result in impaired pollen walls that lack a normal exine layer and exhibit a characteristic striped surface, termed zebraphenotype. Heterologous expression of CYP704B1 in yeast cells demonstrated that it catalyzes v-hydroxylation of long-chainfatty acids, …
Incidence And Post-Pollination Mechanisms Of Nonrandom Mating In Arabidopsis Thaliana, Ann L. Carlson, Megan Telligman, Rob Swanson
Incidence And Post-Pollination Mechanisms Of Nonrandom Mating In Arabidopsis Thaliana, Ann L. Carlson, Megan Telligman, Rob Swanson
Biology Faculty Publications
Compatible pollinations from many differenttaxa display nonrandom mating. Here we describe a systemfor examining questions of nonrandom mating in Arabidopsisthaliana. Using this system, we demonstrate thatArabidopsis thaliana displays nonrandom mating betweendistinct accessions. Statistical analysis of these data demonstratesaspects of both pollen competition and male–female complementarity in these matings. Cytologicalexperiments implicate pollen germination and pollen tubegrowth rates as possible causal factors in these nonrandommating efficiencies.
Lap3, A Novel Plant Protein Required For Pollen Development, Is Essential For Proper Exine Formation, Anna A. Dobritsa, Shuh-Ichi Nishikawa, Daphne Preuss, Ewa Urbanczyk-Wochniak, Lloyd W. Sumner, Adam Hammond, Ann L. Carlson, Rob Swanson
Lap3, A Novel Plant Protein Required For Pollen Development, Is Essential For Proper Exine Formation, Anna A. Dobritsa, Shuh-Ichi Nishikawa, Daphne Preuss, Ewa Urbanczyk-Wochniak, Lloyd W. Sumner, Adam Hammond, Ann L. Carlson, Rob Swanson
Biology Faculty Publications
We isolated lap3-1 and lap3-2 mutants in ascreen for pollen that displays abnormal stigma binding.Unlike wild-type pollen, lap3-1 and lap3-2 pollen exine isthinner, weaker, and is missing some connections betweentheir roof-like tectum structures. We describe the mappingand identification of LAP3 as a novel gene that contains arepetitive motif found in b-propeller enzymes. Insertionmutations in LAP3 lead to male sterility. To investigatepossible roles for LAP3 in pollen development, we assayedthe metabolite profile of anther tissues containing developingpollen grains and found that the lap3-2 defect leadsto a broad range of metabolic changes. The largest changeswere seen in levels of a straight-chain hydrocarbon …
In Vitro Guidance Of Retinal Axons By A Tectal Lamina-Specific Glycoprotein Nel, Yulan Jiang, Hiroya Obama, Soh-Leh Kuan, Ritsuko Nakamura, Chizu Nakamoto, Zhufeng Ouyang, Masaru Nakamoto
In Vitro Guidance Of Retinal Axons By A Tectal Lamina-Specific Glycoprotein Nel, Yulan Jiang, Hiroya Obama, Soh-Leh Kuan, Ritsuko Nakamura, Chizu Nakamoto, Zhufeng Ouyang, Masaru Nakamoto
Biology Faculty Publications
Nel is a glycoprotein containing five chordin-like and six epidermal growth factor-like domains and is strongly expressed in the nervous system. In this study, we have examined expression patterns and in vitro functions of Nel in the chicken retinotectal system. We have found that in the developing tectum, expression of Nel is localized in specific laminae that retinal axons normally do not enter, including the border between the retinorecipient and non-retinorecipient laminae. Nel-binding activity is detected on retinal axons both in vivo and in vitro, suggesting that retinal axons express a receptor for Nel. In vitro, Nel inhibits retinal axon …
Strain-Dependent Relationship Between Growth Rate And Hyphal Branching In Neurospora Crassa, Michael K. Watters, Erik Lindamood, Margaret Meunich, Ryan Vetor
Strain-Dependent Relationship Between Growth Rate And Hyphal Branching In Neurospora Crassa, Michael K. Watters, Erik Lindamood, Margaret Meunich, Ryan Vetor
Biology Faculty Publications
In a previous study of branch frequency in Neurospora crassa focused on the wild-type, no relationship between growth rate and the frequency of hyphal branching was observed. In subsequent experiments, it became clear that while this independence is valid for the wild type and most mutant strains, it fails to hold for a subset of morphological mutants. This study distinguishes a subset of Neurospora morphological mutants for their morphological response to altered growth rate. Growth rates are altered using two different methods: reduced temperature and nutrient-deficient media. This should assure that the observed effect is not due to simple conditional …
Neuronal Pentraxins Mediate Synaptic Refinement In The Developing Visual System, Lisa Bjartmar, Andrew Huberman, Erik Ullian, Rene Renterıa, Xiaoqin Liu, Weifeng Xu, Jennifer Prezioso, Michael Susman, David Stellwagen, Caleb Stokes, Richard Cho, Paul Worley, Robert Malenka, Sherry Ball, Neal Peachey, David Copenhagen, Barbara Chapman, Masaru Nakamoto, Ben Barres, Mark Perin
Neuronal Pentraxins Mediate Synaptic Refinement In The Developing Visual System, Lisa Bjartmar, Andrew Huberman, Erik Ullian, Rene Renterıa, Xiaoqin Liu, Weifeng Xu, Jennifer Prezioso, Michael Susman, David Stellwagen, Caleb Stokes, Richard Cho, Paul Worley, Robert Malenka, Sherry Ball, Neal Peachey, David Copenhagen, Barbara Chapman, Masaru Nakamoto, Ben Barres, Mark Perin
Biology Faculty Publications
Neuronal pentraxins (NPs) define a family of proteins that are homologous to C-reactive and acute-phase proteins in the immune system and have been hypothesized to be involved in activity-dependent synaptic plasticity. To investigate the role of NPs in vivo , we generated mice that lack one, two, or all three NPs. NP1/2 knock-out mice exhibited defects in the segregation of eye-specific retinal ganglion cell (RGC) projections to the dorsal lateral geniculate nucleus, a process that involves activity-dependent synapse formation and elimination. Retinas from mice lacking NP1 and NP2 had cholinergically driven waves of activity that occurred at a frequency similar …
Callose (Β-1,3 Glucan) Is Essential For Arabidopsis Pollen Wall Patterning, But Not Tube Growth, Rob Swanson
Callose (Β-1,3 Glucan) Is Essential For Arabidopsis Pollen Wall Patterning, But Not Tube Growth, Rob Swanson
Biology Faculty Publications
Background: Callose (β-1,3 glucan) separates developing pollen grains, preventing their underlying walls (exine) from fusing. The pollen tubes that transport sperm to female gametes also contain callose, both in their walls as well as in the plugs that segment growing tubes. Mutations in CalS5, one of several Arabidopsis β-1,3 glucan synthases, were previously shown to disrupt callose formation around developing microspores, causing aberrations in exine patterning, degeneration of developing microspores, and pollen sterility. Results: Here, we describe three additional cals5 alleles that similarly alter exine patterns, but instead produce fertile pollen. Moreover, one of these alleles (cals5-3) resulted in the …
Biphasic Functions Of The Kinase-Defective Ephb6 Receptor In Cell Adhesion And Migration, Hiroshi Matsuoka, Hiroya Obama, Meghan Kelly, Toshimitsu Matsui, Masaru Nakamoto
Biphasic Functions Of The Kinase-Defective Ephb6 Receptor In Cell Adhesion And Migration, Hiroshi Matsuoka, Hiroya Obama, Meghan Kelly, Toshimitsu Matsui, Masaru Nakamoto
Biology Faculty Publications
EphB6 is a unique member in the Eph family of receptor tyrosine kinases in that its kinase domain contains several alterations in conserved amino acids and is catalytically inactive. Although EphB6 is expressed both in a variety of embryonic and adult tissues, biological functions of this receptor are largely unknown. In the present study, we examined the function of EphB6 in cell adhesion and migration. We demonstrated that EphB6 exerted biphasic effects in response to different concentrations of the ephrin-B2 ligand; EphB6 promoted cell adhesion and migration when stimulated with low concentrations of ephrin-B2, whereas it induced repulsion and inhibited …
Loss-Of-Function Analysis Of Epha Receptors In Retinotectal Mapping, David Feldheim, Masaru Nakamoto, Miriam Osterfield, Nicholas Gale, Thomas Dechiara, Rajat Rohatgi, George Yancopoulos, John Flanagan
Loss-Of-Function Analysis Of Epha Receptors In Retinotectal Mapping, David Feldheim, Masaru Nakamoto, Miriam Osterfield, Nicholas Gale, Thomas Dechiara, Rajat Rohatgi, George Yancopoulos, John Flanagan
Biology Faculty Publications
EphA tyrosine kinases are thought to act as topographically specific receptors in the well-characterized projection map from the retina to the tectum. Here, we describe a loss-of-function analysis of EphA receptors in retinotectal mapping. Expressing patches of a cytoplasmically truncated EphA3 receptor in chick retina caused temporal axons to have reduced responsiveness to posterior tectal repellent activity in vitro and to shift more posteriorly within the map in vivo . A gene disruption of mouse EphA5, replacing the intracellular domain with beta-galactosidase, reduced in vitro responsiveness of temporal axons to posterior target membranes. It also caused map abnormalities in vivo …
Diverse Roles For The Eph Family Of Receptor Tyrosine Kinases In Carcinogenesis, Masaru Nakamoto, Andrew Bergeman
Diverse Roles For The Eph Family Of Receptor Tyrosine Kinases In Carcinogenesis, Masaru Nakamoto, Andrew Bergeman
Biology Faculty Publications
The Eph family of receptor tyrosine kinases and their cell-presented ligands, the ephrins, are frequently overexpressed in a wide variety of cancers, including breast, small-cell lung and gastrointestinal cancers, melanomas, and neuroblastomas. In particular, one Eph family member, EphA2, is overexpressed in many cancers, including 40% of breast cancers. EphA2 can also transform breast epithelial cells in vitro to display properties commonly associated with the development of metastasis. Remarkably, the oncogenic properties of EphA2 contravene traditional dogma with regard to the oncogenic properties of a growth factor and its receptor tyrosine kinase: while stimulation of EphA2 by its ligand (ephrin-A1) …
Domain-Specific Olivocerebellar Projection Regulated By The Epha-Ephrin-A Interaction, Kazuhiko Nishida, John Flanagan, Masaru Nakamoto
Domain-Specific Olivocerebellar Projection Regulated By The Epha-Ephrin-A Interaction, Kazuhiko Nishida, John Flanagan, Masaru Nakamoto
Biology Faculty Publications
Neural maps in the vertebrate central nervous system often show discontinuously segregated, domain-to-domain patterns. However, the molecular mechanism that establishes such maps is not well understood. Here we show that in the chicken olivocerebellar system, EphA receptors and ephrin-As are expressed with distinct levels and combinations in mapping domains. When ephrin-A2 is retrovirally overexpressed in the cerebellum, the olivocerebellar map is disrupted, excluding axons with high receptor activity from ectopic expression domains. Conversely, overexpression of a truncated EphA3 receptor in the cerebellum reduces endogenous ligand activity to undetectable levels and causes aberrant mapping, with high receptor axons invading high ligand …
A Conserved Ubiquitin Ligase Of The Nuclear Envelope/Endoplasmic Reticulum That Functions In Both Er-Associated And Mat A2 Repressor Degradation, Rob Swanson
Biology Faculty Publications
Substrate discrimination in the ubiquitin–proteasome system is believed to be dictated by specific combinations of ubiquitin–protein ligases (E3s) and ubiquitin-conjugating enzymes (E2s). Here we identify Doa10/Ssm4 as a yeast E3 that is embedded in the endoplasmic reticulum (ER)/nuclear envelope yet can target the soluble transcription factor Mat2. Doa10 contains an unusual RING finger, which has ubiquitin-ligase activity in vitro and is essential in vivo for degradation of 2 via its Deg1 degradation signal. Doa10 functions with two E2s, Ubc6 and Ubc7, to ubiquitinate Deg1-bearing substrates, and it is also required for the degradation of at least one ER membrane protein. …
Eph Receptors And Ephrins, Masaru Nakamoto
Eph Receptors And Ephrins, Masaru Nakamoto
Biology Faculty Publications
The Eph receptors are the largest known family of receptor tyrosine kinases. The Eph receptors and theirmembrane-attached ligands, ephrins, show diverse expression patterns during development. Recent studies havedemonstrated that Eph receptors and ephrins play important roles in many developmental processes, includingneuronal network formation, the patterning of the neural tube and the paraxial mesoderm, the guidance of cellmigration, and vascular formation. In the nervous system, Eph receptors and ephrins have been shown to act aspositional labels to establish topographic projections. They also play a key role in pathway ®nding by axons andneural crest cells. The crucial roles of Eph receptors and …
Topographically Specific Effects Of Elf-1 On Retinal Axon Guidance In Vitro And Retinal Axon Mapping In Vivo, Masaru Nakamoto
Topographically Specific Effects Of Elf-1 On Retinal Axon Guidance In Vitro And Retinal Axon Mapping In Vivo, Masaru Nakamoto
Biology Faculty Publications
Topographic maps, which maintain the spatial order of neurons in the order of their axonal connections, are found throughout the nervous system. In the visual retinotectal projection, ELF-1, a ligand in the tectum, and its receptors in the retina show complementary gradients in expression and binding, indicating they may be positional labels for map development. Here we show that ELF-1 acts as a repellent axon guidance factor in vitro. In vivo, when the tectal ELF-1 pattern is modified by retroviral overexpression, retinal axons avoid ectopic ELF-1 patches and map to abnormally anterior positions. All these effects were seen on axons …
Complementary Gradients In Expression And Binding Of Elf-1 And Mek4 In Development Of The Topographic Retinotectal Projection Map, Masaru Nakamoto
Complementary Gradients In Expression And Binding Of Elf-1 And Mek4 In Development Of The Topographic Retinotectal Projection Map, Masaru Nakamoto
Biology Faculty Publications
Topographic maps with a defined spatial ordering of neuronal connections are a key feature of brain organization. Such maps are believed to develop in response to complementary position-specific labels in presynaptic and postsynaptic fields. However, the complementary labeling molecules are not known. In the well studied visual map of retinal axons projecting to the tectum, the labels are hypothesized to be in gradients, without needing large numbers of cell-specific molecules. We recently cloned ELF-1 as a ligand for Eph family receptors. Here, RNA hybridization shows matching expression gradients for ELF-1 in the tectum and its receptor Mek4 in the retina. …
Mouse Heparin Binding Protein-44 (Hbp-44) Associates With Brushin, A High-Molecular-Weight Glycoprotein Antigen Common To The Kidney And Teratocarcinomas, Masaru Nakamoto, Masayuki Ozawa, Sonia Jacinto, Tatsuhiko Furukawa, Yasuhiro Natori, Hiroshi Shirahama, Suguru Yonezawa, Tatsuo Nakayama, Takashi Muramatsu
Mouse Heparin Binding Protein-44 (Hbp-44) Associates With Brushin, A High-Molecular-Weight Glycoprotein Antigen Common To The Kidney And Teratocarcinomas, Masaru Nakamoto, Masayuki Ozawa, Sonia Jacinto, Tatsuhiko Furukawa, Yasuhiro Natori, Hiroshi Shirahama, Suguru Yonezawa, Tatsuo Nakayama, Takashi Muramatsu
Biology Faculty Publications
Heparin binding protein-44 (HBP-44) is a heparin binding protein of 44 kDa, found by cDNA cloning using antibodies against teratocarcinoma glycoproteins [Furukawa, T. et al. (1990) J. Biochem. 108, 297-302]. The N-terminal sequence analysis reported in this publication establishes the structure of its mature form. Immunohistochemical staining revealed that HBP-44 was located in the tubular brush border of the kidney. HBP-44 formed a complex with brushin, a high molecular weight (460 kDa) glycoprotein antigen common to the kidney and teratocarcinoma, but not with OR8 antigen, another antigen (350 kDa) of the same category. Brushin was shown to be the mouse …
A New Family Of Heparin Binding Growth/Differentiation Factors: Differential Expression Of The Midkine (Mk) And Hb-Gam Genes During Mouse Development, Masaru Nakamoto, Shyuichiro Matsubara, Teruo Miyauchi, Hiroya Obama, Takashi Muramatsu
A New Family Of Heparin Binding Growth/Differentiation Factors: Differential Expression Of The Midkine (Mk) And Hb-Gam Genes During Mouse Development, Masaru Nakamoto, Shyuichiro Matsubara, Teruo Miyauchi, Hiroya Obama, Takashi Muramatsu
Biology Faculty Publications
MK (midkine) and HB-GAM (heparin-binding growth-associated molecule) constitute a new family of heparin-binding growth differentiation factors. The modes of expression of MK and HB-GAM during mouse development were quantitatively examined by mRNA hybridization. The following three distinct patterns of expression were observed in the brain/head region. On the 11th-13th days of gestation, MK was intensely, but HB-GAM relatively weakly expressed; on the 15th-19th days, both MK and HB-GAM expression became weaker; and in the neonatal period, HB-GAM was intensely expressed and MK expression increased slightly. The level of HB-GAM expression was lower than that of MK in the whole embryo …
A Retinoic Acid Responsive Gene, Mk, Produces A Secreted Protein A With Heparin Binding Activity, Masaru Nakamoto
A Retinoic Acid Responsive Gene, Mk, Produces A Secreted Protein A With Heparin Binding Activity, Masaru Nakamoto
Biology Faculty Publications
MK is a gene whose expression increases transiently during retinoic acid-induced differentiation of embryonal carcinoma cells. MK polypeptide was secreted by differentiating HM-1 embryonal carcinoma cells and by L-cells transfected with an MK cDNA under the control of the S-actin promoter and Rous sarcoma virus enhancer. MK polypeptide was found to have heparin binding activity. Conditioned medium of the transfected L-cells promoted growth of PC-12 pheochromocytoma cells. These findings support the view that MK polypeptide is a secreted factor involved in regulation of growth and differentiation.