Competition between noggin and bone morphogenetic protein 4 activities may regulate dorsalization during Xenopus development.

Re'Em-Kalma, Yael; Lamb, Teresa M.; Frank, Dale

doi:10.1073/pnas.92.26.12141

Cited by 147 publications

(103 citation statements)

References 33 publications

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“…Many studies have shown that BMP4 is a secreted protein capable of acting over distances as a morphogen in multiple species (Harland, 1994;Re'em-Kalma et al, 1995;Dosch et al, 1997;Gerlach et al, 2000; for reviews of BMP4 activity, see Hogan, 1996;Hild et al, 2000). It is possible that DAN may act as an additional antagonist of BMP activity, complementing that of noggin, but that DAN has a specific functional role during inner ear development separate from that of its inhibition of BMPs.…”

Section: Discussionmentioning

confidence: 99%

DAN directs endolymphatic sac and duct outgrowth in the avian inner ear

Gerlach-Bank

Cleveland

Barald

2003

Developmental Dynamics

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Bone morphogenetic proteins (BMPs) are expressed in the developing vertebrate inner ear and participate in inner ear axial patterning and the development of its sensory epithelium. BMP antagonists, such as noggin, chordin, gremlin, cerberus, and DAN (differential screening-selected gene aberrative in neuroblastoma) inhibit BMP activity and establish morphogenetic gradients during the patterning of many developing tissues and organs. In this study, the role of the BMP antagonist DAN in inner ear development was investigated. DAN-expressing cell pellets were implanted into the otocyst and the periotic mesenchyme to determine the effects of exogenous DAN on otic development. Similar to the effects on the inner ear seen after exposure of otocysts to the BMP4 antagonist noggin, semicircular canals were truncated or eliminated based upon the site of pellet implantation. Unique to the DAN implantations, however, were effects on the developing endolymphatic duct and sac. In DAN-treated inner ears, endolymphatic ducts and sacs were merged with the crus or grew into the superior semicircular canal. Both the canal and endolymphatic duct and sac effects were rescued by joint implantation of BMP4-expressing cells.

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Section: Discussionmentioning

confidence: 99%

DAN directs endolymphatic sac and duct outgrowth in the avian inner ear

Gerlach-Bank

Cleveland

Barald

2003

Developmental Dynamics

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“…Shi et al (2002) reported that the Wnt/beta-catenin pathway is required for regulating myogenic gene expression in the presumptive mesoderm and may directly activate the expression of the XMyf-5 gene in the muscle precursor cells. XMyoD was also transiently transcribed in BMP-4 -injected animal caps, and in BMP-4 -injected whole embryos, XMyoD transcripts were increased (Re'em-Kalma et al, 1995). Dosch et al (1997) showed that XMyf-5 expression and muscle differentiation require a low dose of BMP-4, resulting from superposition of antagonizing BMP-4 and noggin proteins in vivo.…”

Section: What Molecular Signals Initiate the Myogenic Program Duringmentioning

confidence: 99%

Xenopusmuscle development: From primary to secondary myogenesis

Chanoine

Hardy

2002

Developmental Dynamics

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Xenopus myogenesis is characterized by specific features, different from those of mammalian and avian systems both at the cellular level and in gene expression patterns. During early embryogenesis, after the initial molecular signals inducing mesoderm, the myogenic determination factors XMyoD and XMyf-5 are activated in presomitic mesoderm in response to mesoderm-inducing factors. After these first inductions of the myogenic program, forming muscles in Xenopus can have different destinies, some of these resulting in cell death before adulthood. In particular, it is quite characteristic of this species that, during metamorphosis, the primary myotomal myofibers completely die and are progressively replaced by secondary "adult" multinucleated myofibers. This feature offers the unique opportunity to totally separate the molecular analysis of these two distinct types of myogenesis. The aim of this review is to summarize our knowledge on the cellular and molecular events as well as the epigenetic regulations involved in the construction of Xenopus muscles during development. Developmental Dynamics 226:12-23, 2003.

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“…Coinjection of neogenin MO and FL-RGMa mRNA prevented the cell spreading that was observed in RGMa-overexpressing animal caps ( RGMa has been proposed to act as a coreceptor for BMPs and to mediate their signaling in vitro (17,60). To address the role of BMP in RGMa-neogenin signaling, we treated animal cap explants with exogenous Noggin, which binds to and blocks BMP activity (44). Noggin (50 to 500 ng/ml) was active in our animal cap assay since it caused the induction of the neuroectoderm marker NCAM (26) (see Fig.…”

Section: Rgma Induces Animal Cap Spreadingmentioning

confidence: 99%

Novel Roles of the Chemorepellent Axon Guidance Molecule RGMa in Cell Migration and Adhesion

Lah

Key

2012

Molecular and Cellular Biology

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The repulsive guidance molecule A (RGMa) is a contact-mediated axon guidance molecule that has significant roles in central nervous system (CNS) development. Here we have examined whether RGMa has novel roles in cell migration and cell adhesion outside the nervous system. RGMa was found to stimulate cell migration from Xenopus animal cap explants in a neogenindependent and BMP-independent manner. RGMa also stimulated the adhesion of Xenopus animal cap cells, and this adhesion was dependent on neogenin and independent of calcium. To begin to functionally characterize the role of specific domains in RGMa, we assessed the migratory and adhesive activities of deletion mutants. RGMa lacking the partial von Willebrand factor type D (vWF) domain preferentially perturbed cell adhesion, while mutants lacking the RGD motif affected cell migration. We also revealed that manipulating the levels of RGMa in vivo caused major migration defects during Xenopus gastrulation. We have revealed here novel roles of RGMa in cell migration and adhesion and demonstrated that perturbations to the homeostasis of RGMa expression can severely disrupt major morphogenetic events. These results have implications for understanding the role of RGMa in both health and disease. Repulsive guidance molecule (RGM) was first identified in the embryonic chick retinotectal system as a chemorepulsive molecule for retinal axons (35). Subsequently, three different RGMs (RGMa, RGMb, and RGMc) were identified in mouse, and each was found to have a unique spatiotemporal expression pattern (41,48). RGMa is a membrane-bound protein with ϳ430 amino acid (aa) residues that has a glycosylphosphatidylinositol (GPI)-anchored C-terminal domain and a conventional N-terminal signal peptide (35,48). It is cysteine rich and contains a putative autoproteolytic cleavage site, a single tri-amino acid motif, ArgGly-Asp (RGD), a partial von Willebrand factor type D (vWF) domain, and two hydrophobic domains at the N and C termini. These key molecular structures, except for the RGD domain (which is absent in RGMb in most animal models), are shared by all members of the RGM family (5, 35). A conserved RSDSPEI sequence, 5= to the partial von Willebrand type D domain, is present within RGMa from mammals, frogs, and birds. To date, the roles of these different RGM domains remain unknown.The first RGM receptor was identified by cell surface binding of chick RGM to cells expressing neogenin, a member of the immunoglobulin superfamily of transmembrane receptors (31,35,43,(54)(55)(56)(57). RGMa-neogenin interactions are involved in axon guidance in the developing visual system and in axon tract formation in the embryonic brain in vivo (31,35,54,55,57,58). RGMa also has chemorepulsive activity during laminar patterning of the developing mouse dentate gyrus in vitro (4). Interestingly, RGMa knockout mice did not show an abnormality in retinal topography but displayed an exencephalic phenotype in ϳ50% of embryos, suggesting that RGMa plays a role in neural tube closure (37). We and others...

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Competition between noggin and bone morphogenetic protein 4 activities may regulate dorsalization during Xenopus development.

Cited by 147 publications

References 33 publications

DAN directs endolymphatic sac and duct outgrowth in the avian inner ear

DAN directs endolymphatic sac and duct outgrowth in the avian inner ear

Xenopusmuscle development: From primary to secondary myogenesis

Novel Roles of the Chemorepellent Axon Guidance Molecule RGMa in Cell Migration and Adhesion

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