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At least 199 records · Page 11Linked to original sources
PubMed2005

Expression of N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) GluR2/3 receptors in the developing rat pineal gland.

The expression of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) type glutamate (GluR2/3) receptors and N-methyl-D-aspartate receptor subtype 1 (NMDAR1) was carried out by immunohistochemistry, double immunofluorescence and real-time RT-PCR analysis in the pineal glands of 1-day to 6-wk-old rats in the present study. GluR2/3 immunopositive cells were distributed throughout the pineal gland and showed branching processes in all age groups. The NMDAR1 immunoreactivity, however, was observed in fewer branched cells. A constitutive mRNA expression of NMDAR1, GluR2 and GluR3 was detected in the pineal glands of various ages and showed no significant difference between the age groups studied. Immunohistochemical and double immunofluorescence results showed that the GluR2/3 were mainly expressed and co-localized with OX-42-positive microglia/macrophages and the glial fibrillary acidic protein (GFAP)-positive astrocytes. Co-localization of NMDAR1 with OX-42- and GFAP-positive cells was much less. The expression of these receptors on the glial cells suggests that they may be involved in the development and growth of the pineal gland in the early postnatal period (1 day to 3 wk) and subsequently in the regulation of melatonin synthesis.

Animals↗
PubMed2003

Non-contractile cells with thin processes resembling interstitial cells of Cajal found in the wall of guinea-pig mesenteric arteries.

Arterial interstitial cells of Cajal (ICC)-like cells (AIL cells) with a multipolar, irregular, elongated shape and with numerous thin (often less than 1 microm), sometimes branching, processes with lengths up to approximately 60 microm were isolated enzymatically from 1st to 7th order branches of guinea-pig mesenteric artery. Some of the processes of AIL cells were growing (average speed approximately 0.15 microm min-1) and their growth was blocked by 10 microM latrunculin B, an inhibitor of actin polymerisation. Staining with BODIPY phalloidin, a fluorescent dye selective for F-actin, showed the presence of F-actin in the processes of AIL cells. Voltage clamp of single AIL cells revealed an inward current that was four times more dense than in myocytes and was abolished by 10 microM nicardipine, and an outward current carried exclusively by potassium ions that was reduced by 1 mM 4-aminopyridine and/or 100 nM iberiotoxin but unaffected by 10 nM dendrotoxin-K. Imaging of intracellular ionised calcium with fluo-4 using a laser scanning confocal microscope showed local or global calcium transients lasting several seconds in approximately 28 % of AIL cells. When membrane current was recorded simultaneously, the calcium transients were found to correspond to long-lasting transient outward currents, which occurred at potentials positive to -40 mV. Unlike myocytes, AIL cells did not contract in response to 1 mM caffeine or 5 microM noradrenaline, although they responded with a [Ca2+]i increase. The segments of intact arteries did not stain for c-kit, a marker of ICCs. Single AIL cells stained positive for vimentin, desmin and smooth muscle myosin. The presence of ICC-like cells is demonstrated for the first time in the media of resistance arteries.

Animals↗
PubMed1991

Homeobox gene expression correlated with the bifurcation process of limb cartilage development.

The complex architecture of the limb cartilage pattern probably develops by the sequential segmentation and branching process of precartilaginous cell condensation under the control of positional signalling provided by the zone of polarizing activity (anteroposterior) and the apical ectodermal ridge (proximodistal). This signalling is monitored and interpreted in the mesenchymal cells and induces the position-specific response of subsets of genes. Homeobox genes may be responsible for the interpretation of signalling. A correlation between limb pattern and expression domains of the homeobox genes in the upstream region of Hox/Chox-4 has been proposed. We have analysed the spatial expression pattern of the Chox-1 genes during development of chick limb buds. In contrast to genes in Hox/Chox-4 expressed coordinately along the anteroposterior axis, homeobox genes in Chox-1 have unique and mutually exclusive expression domains along the proximodistal axis. We report here that the expression domains of the Chox-1 genes are closely related to the segmental structure of cartilage along the proximodistal axis, whereas the expression domains of the Chox-4 genes are related to the cartilage branching pattern.

Animals↗
PubMed2001

Neu differentiation factor regulates tau protein and mRNA in cultured neonatal oligodendrocytes.

Axonal signals activate myelinogenesis via regulation of the extent to which oligodendrocyte (OLG) processes wrap around the axon. The cytoskeleton in OLG processes is actively involved in myelination and is a putative target for axonal regulation of myelination. The axon-associated neuregulins may regulate the cytoskeleton extensions in OLG processes. Here, we report that the neuregulin neu differentiation factor (NDF) increases the expression of tau mRNA and tau protein in OLGs. Treatment of neonatal OLGs with alpha-NDF or beta-NDF resulted in dramatic increases in the length of OLG processes, which appeared either as singular unbranched extensions or as a network of extensively branched processes. By immunoblot analysis with tau-1 mAb, which recognizes the dephosphorylated form of the tau proteins, neonatal OLGs treated with alpha-NDF or beta-NDF, had an increase in tau protein levels. The increase of tau levels in beta-NDF-treated cells is much greater than the twofold increase present in alpha-NDF-treated cells. By immunoblot analysis with the phosphorylation-insensitive tau-5 mAb, beta-NDF-treated cells had a twofold increase in tau. Immunoblot analysis suggest that alpha-NDF and beta-NDF promote a twofold increase in the tau protein levels in OLG, with the beta-factor also promoting a tau dephosphorylation. Using promoters spanning the amino-terminal region of tau, we found that OLGs treated with alpha-NDF or beta-NDF contained approximately twofold more tau mRNA than untreated cells. However, there was no qualitative difference between control and NDF-treated cells in the pattern of tau mRNA isoforms expressed. A model is proposed in which the axonal NDF-induced regulation of tau expression in OLGs may be part of the mechanism by which the axon regulates myelination.

Animals↗
PubMed1997

Morphological evidence for local microcircuits in rat vestibular maculae.

Previous studies suggested that intramacular, unmyelinated segments of vestibular afferent nerve fibers and their large afferent endings (calyces) on type I hair cells branch. Many of the branches (processes) contain vesicles and are presynaptic to type II hair cells, other processes, intramacular nerve fibers, and calyces. This study used serial section transmission electron microscopy and three-dimensional reconstruction methods to document the origins and distributions of presynaptic processes of afferents in the medial part of the adult rat utricular macula. The ultrastructural research focused on presynaptic processes whose origin and termination could be observed in a single micrograph. Results showed that calyces had 1) vesiculated, spine-like processes that invaginated type I cells and 2) other, elongate processes that ended on type II cells pre- as well as postsynaptically. Intramacular, unmyelinated segments of afferent nerve fibers gave origin to branches that were presynaptic to type II cells, calyces, calyceal processes, and other nerve fibers in the macula. Synapses with type II cells occurred opposite subsynaptic cisternae (C synapses); all other synapses were asymmetric. Vesicles were pleomorphic but were differentially distributed according to process origin. Small, clear-centered vesicles, approximately 40-60 nm in diameter, predominated in processes originating from afferent nerve fibers and basal parts of calyces. Larger vesicles approximately 70-120 nm in diameter having approximately 40-80 nm electron-opaque cores were dominant in processes originating from the necks of calyces. Results are interpreted to indicate the existence of a complex system of intrinsic feedforward (postsynaptic)-feedback (presynaptic) connections in a network of direct and local microcircuits. The morphological findings support the concept that maculae dynamically preprocess linear acceleratory information before its transmission to the central nervous system.

Acoustic Maculae↗
PubMed1980

Capsules of duck muscle spindles.

Duck muscle spindles show a large outer capsule enclosing a number of intrafusal muscle fibres which are individually encircled by an inner capsule. The outer capsule consists of a multilayer of 4-6 flattened cells with elongated nuclei, and are usually lined by a basement membrane. They resemble and are linked with perineural cells of the nerve bundle that innervates the spindle. There is overlapping and interdigitation between branching processes of these cells. Some apposing surfaces develop junctional complexes in the form of hemi-desmosomes and desmosomes. The cytoplasmic content shows numerous pinocytotic vesicles, some polyribosomes, lamellated cisternae of rough endoplasmic reticulum and microfilaments. The inner capsule consists of cells showing, at the mid-equatorial region, a large ovoid nucleus and extensive branching of thin and long processes that overlap, forming numerous layers around each intrafusal muscle fibre. Bundles of collagen fibrils in a crescent-shaped configuration occur circumferentially between the multilayer of processes and the muscle fibre. Some linkages between the inner and the outer capsule cell processes provide a network that subdivides the large periaxial space into compartments. There is no basement material lining the inner capsule cells and the processes. Some cytoplasmic area occurs around the ovoid nucleus and the cytoplasm varies in density, showing some dilated short profiles of rough endoplasmic reticulum, a few pinocytotic vesicles and microfilaments.

Animals↗
PubMed2003

Some glial progenitors in the neonatal subventricular zone migrate through the corpus callosum to the contralateral cerebral hemisphere.

The great majority of glial cells of the mammalian forebrain are generated in the perinatal period from progenitors in the subventricular zone (SVZ). We investigated the migration of progenitors from the neonatal (postnatal day 0, P0) rat forebrain SVZ by labeling them in vivo with a green fluorescence protein (GFP) retrovirus and monitoring their movements by time-lapse video microscopy in P3 slices. We identified a small number of progenitors that migrated tangentially within the corpus callosum (CC) and crossed the midline. These cells retained a relatively uniform morphology: the leading process was extended toward the contralateral side but showed no process branching or turning away from the migratory direction. Net migration requires the elongation of the leading process and nuclear translocation, and the migrating cells in the CC showed both modes. We confirmed the presence of unmyelinated axon bundles within the P3 CC, but failed to detect any radially directed glial processes (vimentin- or GLAST-immunolabeled fibers) spanning through the CC. Confocal images showed a close proximity between neurofilament-immunolabeled axons and the leading process of the GFP-expressing progenitors in the CC. The destination of the callosal fibers was examined by applying DiI to the right cingulum; the labeled fibers ran throughout the CC and reached the left cingulate and motor areas. The distribution and final fates of the retrovirus-labeled cells were examined in P28 brains. A small proportion of the labeled cells were found in the contralateral hemisphere, where, as oligodendrocytes and astrocytes, they colonized predominantly the cortex and the underlying white matter of the cingulate and secondary motor areas. The distribution pattern appears to coincide well with the projection direction of the callosal fibers. Thus, glial progenitors migrate across the CC, presumably in conjunction with unmyelinated axons, to colonize the contralateral hemisphere.

Animals↗
PubMed1989

Monoclonal antibody markers for amphibian oligodendrocytes and neurons.

Few immunocytochemical probes have been developed for cold-blooded vertebrates, thus hampering analyses of cellular processes in these species. Those developed from mammalian and avian tissue often fail either to react or to show similar specificities in poikilotherms. Therefore, we have begun raising monoclonal antibodies (mabs) in mice against frog and tadpole brain tissue. The following analyses of two of these mabs suggest that these antibodies represent specific probes for frog axons and oligodendrocytes. Mab Olig recognizes all the myelinated axon tracts of the mature frog brain and spinal cord, as well as the tracts of the developing tadpole CNS once they have become myelinated. Axons cut in cross section show characteristic o-shaped staining around individual axons when processed with this antibody. Particularly easy to visualize in the tadpole are immunoreactive cell bodies and processes, seen in continuity with the myelin sheath. Occasionally, in this developing tissue, cells with highly branched processes characteristic of immature oligodendrocytes are observed. No other cells or processes within the brain or spinal cord react with this antibody. Mab Linc stains numerous filaments in all axonal projections. Occasionally, a thin rim of filamentous staining is observed in cell somata, but many regions rich in neuronal somata or dendrites are unreactive to this antibody. This in vivo staining pattern suggests that the Linc antigen is differentially distributed within neurons and exhibits a high concentration in axons. Linc immunoreactivity is robust in the processes of a subpopulation of dissociated tectal cells in culture. These Linc-positive cells are characterized as neurons on morphological criteria. Also, intense Linc immunoreactivity is present in the bundles of retinal axons that extend from retinal explants. Olig immunoreactivity, however, has not been detected in tectal cultures or retinal explants. Improved staining following Triton X-100 treatment of tissue sections suggests that neither of the mabs recognizes lipid antigens and that both are probably localized within the cell cytoplasm. Only the Linc mab reacts on Western blots of denatured brain protein. Linc consistently recognizes two Triton X-100-insoluble proteins with apparent molecular weights of 56 and 58 kD. The epitopes recognized by the Olig and Linc mabs have been surveyed in terms of their resistance to optic nerve crush and their consequent value in studies requiring such procedures. Possible homologies to known cell-type-specific molecules are discussed.

Animals↗
PubMed1988

Effect of polylysine-bound laminin on human retinoblastoma cell lines.

We have studied the responses of three human retinoblastoma cell lines (GM1232, Y79, and WERI-Rb1) to substratum-bound laminin (LN), fibronectin (FN), or collagen (CN) in serum-containing medium. About 95% of the cells attached to poly-D-lysine (PN)-pretreated plastic surfaces either unbound or protein-bound within 1 h after plating. With PN-bound LN, GM1232 cells showed an outgrowth of processes and cell spread within 1 d, but very little was seen on PN-bound FN, CN, or unbound PN even by Day 4. Both the percentage of cells with processes and the number of processes/cell were dependent on the amount of LN bound to the surfaces at Day 4. On LN surfaces without PN pretreatment, by Day 2 most cells had formed floating aggregates and were not attached to the surfaces. By Day 4 only a part of the peripheral cells of attached aggregates displayed process outgrowth and cell spreading. Dibutyryl cyclic AMP (dbcAMP) maintained these effects of PN-bound LN, and promoted process branching, cell spreading, and elongation with concomitant inhibition of cell growth. The percentage of cells with processes was 83%. Y79 and WERI-Rb1 cells, passed for several years, showed little and weak response to PN-bound LN either in the absence or presence of dbcAMP. These results indicate that the morphologic differentiation of GM1232 cells is elicited specifically by PN-bound LN, and that dbcAMP maintains and promotes this differentiated status.

Bucladesine↗
PubMed1998

Morphological forms and localization of microglial cells in the developing human cerebellum.

There are relatively few studies on microglia of human developing brain thus function and location of these cells at this period of life are unknown. Moreover, all of them concentrated on the cells in very early period of fetal life. To achieve further insight into the participation of microglial cells in the development of the central nervous system the brains of fetuses, newborns and infants were examined by means of immunological markers: Ricinus communis agglutinin-1 (RCA-1) and ferritin antiserum. Brains of 12 fetuses and infants ranging in age from 14 weeks of gestation to 5 months after birth were used in the study. The fetuses were derived following spontaneous abortions. In pre-term and term newborns the cause of death was of maternal origin (placental insufficiency) or accidental sudden death. Coronal blocks of cerebellum cut into 5 microns thick sections were used in the study. The developing microglial cells were detected by both markers (RCA-1 and anti-ferritin). Ricinus communis agglutinin recognizes carbohydrate residues on the surfaces of microglial and endothelial cells. Therefore, in the sections incubated with this lectin brain vessels as well as microglia were visualized. The second microglial marker anti-ferritin serum detected precisely all morphological subpopulations of microglia including ameboid and ramified cells but endothelial cells remained immunonegative. Therefore, in 14 weeks of gestation only round ameboid microglia were ferritin-immunopositive in cerebellum. These cells were localized at the periphery of the periventricular, germinal matrix and were surrounding a group of nerve cells of the developing dentate nucleus. In 16 week-old fetuses ameboid cells were present in the hilus and between gyri of the dentate nucleus. The ferritin-positive microglial cells on the convolutions of the dentate nucleus gyri manifested as the cells with short fine branched processes and scanty cytoplasm. In cerebellum of the 20 week-old fetuses the subpopulation of branched (ramified) microglia were more numerous than ameboid cells. Ameboid cells were present mainly in the intermediate zone of the future white matter and ramified cells penetrated the inner (at the one third of its thickness) part of the developing internal granular layer of cerebellar cortex. The upper part of cerebellar cortex was colonized by microglia between 24-28 weeks of gestation. In cerebellum of fetuses over 28 weeks of gestation numerous microglial cells infiltrated mainly the Purkinje cell layer, first in the vermis, later in the hemispheres. From 36 weeks of gestation to the birth ferritin-immunopositive microglial cells gradually disappeared from the cerebellar cortex. The microglia of the term newborns and of a 5 month-old child manifested mainly as ramified cells located in the white matter. The results of our study lead to the conclusion that the localization of microglial cells in the brain structure and their morphological forms correlate precisely with the appropriate stages of the brain development.

Cell Death↗
PubMed1981

Morphological analysis of astrocytes in the bullfrog (Rana catesbeiana) spinal cord with special reference to the site of attachment of their processes.

An attempt was made to elucidate the morphological features of astrocytes in the bullfrog spinal cord by means of a combination of electron microscopy, the Golgi method, and the intravascular dye injection method. Astrocytic somata are densely concentrated both in the wall of the central canal and in its proximity, and diffusely distributed in the intermediate and the ventral part of the gray matter. The most complicated and densest vascular network is found in the dorsal part of the gray matter. There is little correlation between the density of the distribution of astrocytic somata and that of the vascular network. Each astrocyte emits one process and ramifies by repeated bifurcations as it approaches the white matter or enters it. All these branching processes reach the pial surface of the spinal cord (the principal processes). Total rostrocaudal extent of their ramification is within 400 micron. A great number of small lateral offshoots (the secondary processes) arise both from the somata and the principal processes. Electron microscopy of vessel walls and the pial surface revealed that the principal processes attach to the subpial basement membrane with a specialized structure, an electron-dense layer, while the secondary processes merely surround blood vessels in a mode of juxtaposition. Comparison between amphibian and mammalian astrocytes is made regarding the site of attachment of their processes.

Animals↗
PubMed2005

Estimating the life-span of oligodendrocytes from clonal data on their development in cell culture.

This paper presents a new method to analyze clonal data on oligodendrocyte development in cell culture. The process of oligodendrocyte generation from precursor cells is modelled as a multi-type Bellman-Harris branching process as suggested in an earlier paper [K. Boucher, A. Zorin, A.Y. Yakovlev, M. Mayer-Proschel, M. Noble, An alternative stochastic model of generation of oligodendrocytes in cell culture, J. Math. Biol. 43 (2001) 22]. This model has been extended to allow for death of oligodendrocytes as well as a dissimilar distribution of the first mitotic cycle duration as compared to the subsequent cycles of precursor cells, which lengths are assumed to be independent and identically distributed random variables. Since the time-span of oligodendrocytes is not directly observable in clonal data, plausible parametric assumptions are invoked to make estimation problems tractable. In particular, the time to cell death follows a two-parameter gamma distribution, while the lapse of time between the event of cell death and the event of cell disintegration is assumed to be exponentially distributed. A simulated pseudo maximum likelihood method for estimation of model parameters has been developed using simulation-based approximations of the expected numbers and variance-covariance matrices for different types of cells. Finite sample properties of the estimation procedure are studied by computer simulations. The proposed method is illustrated with an analysis of the clonal development of O-2A progenitor cells isolated from the rat optic nerve and the corpus callosum.

Animals↗
PubMed2002

Visualization and force measurement of branching by Arp2/3 complex and N-WASP in actin filament.

To determine whether the Arp2/3 complex activated by N-WASP (VCA) branches actin filaments at the side (side branching), or at the barbed (B-)end (end branching) of the mother filaments, we have directly observed the branching process of actin filaments and examined single-molecule unbinding under optical microscope. We found that side branching was predominant, though not exclusive. At the initial stage of polymerization, the branching at the B-end occurred and subsequently the side branching started to occur. In either type of branching, the mother and daughter filaments elongated at nearly the same rate (growing type). Independently of the stage of polymerization, branching due to the direct coupling of filaments with an acute angle to the mother filaments (a coupling type) occurred. Phalloidin suppressed the growing type of branching but not the coupling type, implying that actin monomers are required for the former but not the latter. We found, by single molecule measurements using optical tweezers, that the Arp2/3 complex attaches to the side of actin filaments and the N-WASP appears to detach from the actin-Arp2/3 complex at 6-7 pN.

Actin-Related Protein 2↗
PubMed1978

A numerical method to model excitable cells.

We have extended a fast, stable, and accurate method for the numerical solution of cable equations to include changes in geometry and membrane properties in order to model a single excitable cell realistically. In addition, by including the provision that the radius may be a function of distance along an axis, we have achieved a general and powerful method for simulating a cell with any number of branched processes, any or all of which may be nonuniform in diameter, and with no restriction on the branching pattern.

Action Potentials↗
PubMed2002

Dynamical random graphs with memory.

We study the large-time dynamics of a Markov process whose states are finite but unbounded graphs. The number of vertices is described by a supercritical branching process, and the edges follow a certain mean-field dynamics determined by the rates of appending and deleting: the older an edge is, the lesser is the probability that it is still in the graph. The lifetime of any edge is distributed exponentially. We call its mean value (common for all edges) a parameter of memory, since it shows for how long the system keeps a particular connection between the vertices in the graph. We show that our model provides a bridge between two well-known models: when the parameter of memory goes to infinity this is a generalized model of random growth, and when this parameter is zero, i.e., no memory, our model behaves as a random graph. Thus by introducing a general class of dynamical graphs we have a unified overview on rather different models and the relations between them. We find all the critical values of the parameters at which our model exhibits phase transitions and describe the properties of the phase diagram. Finally, we compare and discuss the efficiency of the corresponding networks.

Journal Article↗
PubMed2003

Involvement of nitric oxide on kainate-induced toxicity in oligodendrocyte precursors.

The vulnerability of oligodendrocytes to excitatory amino acids may account for the pathology of white matter occurring following hypoxia/ischemia or autoimmune attack. Here, we examined the vulnerability of immature oligodendrocytes (positively labeled by galactocerobroside-C and not expressing myelin basic protein) from neonatal rat spinal cord to kainate, an agonist of excitatory amino acid receptors that induces long-lasting inward currents in immature oligodendrocytes. In particular, we studied whether kainate toxicity was linked to the endogenous production of nitric oxide. We found cultured oligodendrocytes to be highly sensitive to 24-48 h exposure to 0.5-1 mM kainate. The toxin induced striking morphological changes in oligodendrocytes, characterized by the disruption of the process network around the cell body and the growth of one or two long, thick and non-branched processes. A longer exposure to kainate resulted in massive death of oligodendrocytes, which was prevented by 6,7, dinitroquinoxaline-2,3-dione (DNQX) (30 micro M), the antagonist of AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic/kainate receptors. Remarkably, we found that those oligodendrocytes displaying bipolar morphology following kainate exposure, also expressed the inducible form of nitric oxide synthase (iNOS) and nitrotyrosine immunoreactivity, suggesting that peroxynitrite could be formed by the reaction of nitric oxide with superoxide. Moreover, kainate toxicity was significantly prevented by addition of the NOS inhibitor nitro-L-arginine methyl ester (L-NAME), further suggesting that nitric oxide-derived oxidants contribute to excitotoxic mechanisms in immature oligodendrocytes.

Animals↗
PubMed2003

Neuronal avalanches in neocortical circuits.

Networks of living neurons exhibit diverse patterns of activity, including oscillations, synchrony, and waves. Recent work in physics has shown yet another mode of activity in systems composed of many nonlinear units interacting locally. For example, avalanches, earthquakes, and forest fires all propagate in systems organized into a critical state in which event sizes show no characteristic scale and are described by power laws. We hypothesized that a similar mode of activity with complex emergent properties could exist in networks of cortical neurons. We investigated this issue in mature organotypic cultures and acute slices of rat cortex by recording spontaneous local field potentials continuously using a 60 channel multielectrode array. Here, we show that propagation of spontaneous activity in cortical networks is described by equations that govern avalanches. As predicted by theory for a critical branching process, the propagation obeys a power law with an exponent of -3/2 for event sizes, with a branching parameter close to the critical value of 1. Simulations show that a branching parameter at this value optimizes information transmission in feedforward networks, while preventing runaway network excitation. Our findings suggest that "neuronal avalanches" may be a generic property of cortical networks, and represent a mode of activity that differs profoundly from oscillatory, synchronized, or wave-like network states. In the critical state, the network may satisfy the competing demands of information transmission and network stability.

Animals↗
PubMed2005

Canonical Wnt signaling negatively regulates branching morphogenesis of the lung and lacrimal gland.

Key gene families such as FGFs and BMPs are important mediators of branching morphogenesis. To understand whether Wnt genes, and in particular, the canonical Wnt signaling pathway also function in the branching process, we have used a combination of experimental and genetic gain and loss of function approaches to perturb the levels of canonical Wnt signaling in two arborized structures, the lung and the lacrimal gland. Here, we show that the addition of Wnt3a conditioned medium or LiCl strongly represses growth and proliferation of the lung and lacrimal gland, a result that was confirmed in vivo using a dominant stable mutation of beta-catenin conditionally expressed in the lacrimal gland epithelium. In agreement with these data, knockdown of Wnt signaling with beta-catenin morpholinos results in a greater number of branches and increased cell proliferation. In addition, we show that canonical Wnt signaling is able to modulate the levels of Fgf10 and suppress BMP-induced proliferation in the lacrimal gland. Thus, canonical Wnt signaling negatively regulates branching morphogenesis providing a balance to FGFs and BMPs which positively regulate this process. This multilayered control of growth and proliferation ensures that branched structures attain the morphology required to function efficiently.

Adherens Junctions↗