scholarly journals ECM-mediated positional cues are able to induce pattern, but not new positional information, during axolotl limb regeneration

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0248051
Author(s):  
Warren A. Vieira ◽  
Shira Goren ◽  
Catherine D. McCusker

The Mexican Axolotl is able to regenerate missing limb structures in any position along the limb axis throughout its life and serves as an excellent model to understand the basic mechanisms of endogenous regeneration. How the new pattern of the regenerating axolotl limb is established has not been completely resolved. An accumulating body of evidence indicates that pattern formation occurs in a hierarchical fashion, which consists of two different types of positional communications. The first type (Type 1) of communication occurs between connective tissue cells, which retain memory of their original pattern information and use this memory to generate the pattern of the regenerate. The second type (Type 2) of communication occurs from connective tissue cells to other cell types in the regenerate, which don’t retain positional memory themselves and arrange themselves according to these positional cues. Previous studies suggest that molecules within the extracellular matrix (ECM) participate in pattern formation in developing and regenerating limbs. However, it is unclear whether these molecules play a role in Type 1 or Type 2 positional communications. Utilizing the Accessory Limb Model, a regenerative assay, and transcriptomic analyses in regenerates that have been reprogrammed by treatment with Retinoic Acid, our data indicates that the ECM likely facilities Type-2 positional communications during limb regeneration.

1988 ◽  
Vol 249 (3) ◽  
pp. 721-726 ◽  
Author(s):  
F J Ballard ◽  
M Ross ◽  
F M Upton ◽  
G L Francis

1. Competitive binding and receptor cross-linking experiments have been used to examine the receptor-ligand interactions between three bovine insulin-like growth factors (IGF) and monolayer cultures of myoblasts and fibroblasts. 2. Labelled IGF-2 bound predominantly to the type 2 receptor with negligible label cross-linked to the type 1 receptor, notwithstanding the ability of IGF-2 to compete effectively for the binding of IGF-1 to the type 1 receptor. Approx. 100-fold higher concentrations of IGF-1 or the N-terminal truncated (des-Gly-Pro-Glu) IGF-1 (-3N:IGF-1) were required to produce competition equivalent to IGF-2. 3. All IGF peptides, but especially IGF-1, enhanced the binding of labelled IGF-2 to the type 2 receptor of lung fibroblasts. This unusual effect was probably a consequence of the displacement of labelled IGF-2 otherwise bound to a medium protein, a conclusion supported by the demonstration of a 38 kDa membrane protein cross-linked to labelled IGF-2. 4. Both IGF-1 and -3N:IGF-1 bound only to the type 1 IGF receptor in L6 myoblasts, rat vascular smooth-muscle cells and human lung fibroblasts. The peptides competed for labelled IGF-1 binding with potencies in the order -3N:IGF-1 greater than IGF-1 greater than IGF-2 much greater than insulin. Since the IGF peptides were equipotent in skin fibroblasts, it was proposed that the apparently higher affinity of -3N:IGF-1 for receptors in the other cell types was instead a consequence of a low affinity of this peptide for the competing 38 kDa binding protein.


As part of our attempts to understand principles that underly organism development, we have been studying the development of the rat optic nerve. This simple tissue is composed of three glial cell types derived from two distinct cellular lineages. Type-1 astrocytes appear to be derived from a monopotential neuroepithelial precursor, whereas type-2 astrocytes and oligodendrocytes are derived from a common oligodendrocyte-type-2 astrocyte (O-2A) progenitor cell. Type-1 astrocytes modulate division and differentiation of O-2A progenitor cells through secretion of platelet-derived growth factor, and can themselves be stimulated to divide by peptide mitogens and through stimulation of neurotransmitter receptors. In vitro analysis indicates that many dividing O-2A progenitors derived from optic nerves of perinatal rats differentiate symmetrically and clonally to give rise to oligodendrocytes, or can be induced to differentiate into type-2 astrocytes. O-2A perinatal progenitors can also differentiate to form a further O-2A lineage cell, the O-2A adult progenitor, which has properties specialized for the physiological requirements of the adult nervous system. In particular, O-2A adult progenitors have many of the features of stem cells, in that they divide slowly and asymmetrically and appear to have the capacity for extended self-renewal. The apparent derivation of a slowly and asymmetrically dividing cell, with properties appropriate for homeostatic maintenance of existing populations in the mature animal, from a rapidly dividing cell with properties suitable for the rapid population and myelination of central nervous system (CNS) axon tracts during early development, offers novel and unexpected insights into the possible origin of self-renewing stem cells and also into the role that generation of stem cells may play in helping to terminate the explosive growth of embryogenesis. Moreover, the properties of O-2A adult progenitor cells are consistent with, and may explain, the failure of successful myelin repair in conditions such as multiple sclerosis, and thus seem to provide a cellular biological basis for understanding one of the key features of an important human disease.


1974 ◽  
Vol 15 (2) ◽  
pp. 321-346 ◽  
Author(s):  
H. MEINHARDT ◽  
A. GIERER

Model calculations are presented for various problems of development on the basis of a theory of primary pattern formation which we previously proposed. The theory involves short-range autocatalytic activation and longer-range inhibition (lateral inhibition). When a certain criterion is satisfied, self-regulating patterns are generated. The autocatalytic features of the theory are demonstrated by simulations of the determination of polarity in the Xenopus retina. General conditions for marginal and internal activation, and corresponding effects of symmetry are discussed. Special molecular mechanisms of pattern formation are proposed in which activator is chemically converted into inhibitor, or an activator precursor is depleted by conversion into activator. The (slow) effects of primary patterns on differentiation can be included into the formalism in a straightforward manner. In conjunction with growth, this can lead to asymmetric steady states of cell types, cell differentiation and proliferation as found, for instance, in growing and budding hydra. In 2 dimensions, 2 different types of patterns can be obtained. Under some assumptions, a single pattern-forming system produces a ‘bristle’ type pattern of peaks of activity with rather regular spacings on a surface. Budding of hydra is treated on this basis. If, however, gradients develop under the influence of a weak external or marginal asymmetry, a monotonic gradient can be formed across the entire field, and 2 such gradient-forming systems can specify ‘positional information’ in 2 dimensions. If inhibitor equilibrates slowly, a spatial pattern may oscillate, as observed with regard to the intracellular activation of cellular slime moulds. The applications are intended to demonstrate the ability of the proposed theory to explain properties frequently encountered in developing systems.


Endocrinology ◽  
2003 ◽  
Vol 144 (12) ◽  
pp. 5537-5544 ◽  
Author(s):  
Bert De Groef ◽  
Nesya Goris ◽  
Lutgarde Arckens ◽  
Eduard R. Kühn ◽  
Veerle M. Darras

Abstract CRH is known as the main stimulator of ACTH release. In representatives of all nonmammalian vertebrates, CRH has also been shown to induce TSH secretion, acting directly at the level of the pituitary. We have investigated which cell types and receptors are involved in CRH-induced TSH release in the chicken (Gallus gallus). Because a lack of CRH type 1 receptors (CRH-R1) on the chicken thyrotropes has been previously reported, two hypotheses were tested using in situ hybridization and perifusion studies: 1) TSH secretion might be induced in a paracrine way involving melanocortins from the corticotropes; and 2) thyrotropes might express another type of CRH-R. For the latter, we have cloned a partial cDNA encoding the chicken CRH-R2. Neither α-melanotropin (α-MSH) nor its powerful analog Nle4,d-Phe7-MSH could mimic the in vitro TSH-releasing effect of ovine CRH. The nonselective melanocortin receptor blocker SHU91199 did not influence CRH- or TRH-induced TSH secretion. On the other hand, we have found that thyrotropes express CRH-R2 mRNA. The involvement of this CRH receptor in the response of thyrotropes to CRH was further confirmed by the fact that TSH release was stimulated by human urocortin III, a CRH-R2-specific agonist, whereas the TSH response to CRH was completely blocked by the CRH-R blocker astressin and the CRH-R2-specific antagonist antisauvagine-30. We conclude that CRH-induced TSH secretion is mediated by CRH-R2 expressed on thyrotropes.


1993 ◽  
Vol 41 (3) ◽  
pp. 415-421 ◽  
Author(s):  
J M Oldham ◽  
A K Hodges ◽  
P N Schaare ◽  
P C Molan ◽  
J J Bass

To determine the cellular location, capacity, and nutritional sensitivity of insulin-like growth factor (IGF) receptors, we measured the in vitro binding of [125I]-IGFs to skeletal muscle using light microscopic autoradiography. Muscle was collected from 8-month lambs that had received high or low nutrition diets (3% and 1.25% of body weight/day in pellets, respectively). Half of each group had also received growth hormone (0.25 mg/kg/day). Cryosections were incubated with [125I]-IGF alone or with unlabeled IGF-1, IGF-2, or insulin to characterize binding sites as probable Type 1 IGF, Type 2 IGF, or insulin receptors. [125I]-IGF-1 was found to bind to blood vessels and Type 1 receptors in connective tissue (p < or = 0.001), but not to muscle fiber or nerves. In muscle from 6-month lambs that were fed or fasted, [125I]-IGF-1 bound to Type 1 receptors in connective tissue (p < or = 0.01 fed; p < or = 0.05 fasted) and muscle fiber (p < or = 0.05). The binding to connective tissue was also greater in fasted than in fed animals (p < or = 0.05). Binding of [125I]-IGF-2 to the Type 2 receptor was located in blood vessels and connective tissue (p < or = 0.01) and did not alter with fasting. Therefore, these experiments have demonstrated that Type 1 and Type 2 receptors vary in their distribution and nutritional sensitivity in skeletal muscle.


2021 ◽  
Author(s):  
Alexandre Grimaldi ◽  
Glenda Evangelina Comai ◽  
Sebastien Mella ◽  
Shahragim Tajbakhsh

How distinct cell fates are manifested by direct lineage ancestry from bipotent progenitors, or by specification of individual cell types within a field of cells is a key question for understanding the emergence of tissues. The interplay between skeletal muscle progenitors and associated connective tissues cells provides a model for examining how muscle functional units are established. Most craniofacial structures originate from the vertebrate-specific neural crest cells except in the dorsal portion of the head, where they arise from cranial mesoderm. Here, using multiple lineage-traced single cell RNAseq, advanced computational methods and in situ analyses, we identify Myf5+ bipotent progenitors that give rise to both muscle and juxtaposed connective tissue. Following this bifurcation, muscle and connective tissue cells retain complementary signalling features and maintain spatial proximity. Interruption of upstream myogenic identity shifts muscle progenitors to a connective tissue fate. Interestingly, Myf5-derived connective tissue cells, which adopt a novel regulatory signature, were not observed in ventral craniofacial structures that are colonised by neural crest cells. Therefore, we propose that an ancestral program gives rise to bifated muscle and connective tissue cells in skeletal muscles that are deprived of neural crest.


1974 ◽  
Vol 14 (3) ◽  
pp. 657-669
Author(s):  
CARYL E. HILL ◽  
JULIE H. CHAMLEY ◽  
G. BURNSTOCK

Sympathetic ganglia from newborn rats and guinea-pigs were grown in modified Rose chambers and examined with scanning electron microscopy after 5-7 days. The cell types seen were macrophages, neurons, glial cells and connective tissue cells. They presented a wide range of surface morphologies and 3-dimensional configurations, from spheroid with an irregular surface to flattened with a smooth surface. The arrangement of the nerve fibres and cells in the outgrowth was essentially 2-layered with connective tissue cells nearest the substrate and nerve fibres, glial cells and macrophages lying over them. The relationships of sympathetic nerve fibres to the different cell types were also investigated. In all cases nerve fibres closely followed the cellular surface contours although the nature of the relationships varied. Fine finger-like cytoplasmic projections were sometimes seen from connective tissue cells and macrophages. The possible role of these structures in adhesion and motility is discussed.


1990 ◽  
Vol 111 (1) ◽  
pp. 209-215 ◽  
Author(s):  
A da Cunha ◽  
L Vitković

Growth-associated protein 43 (GAP-43) is an abundant, intensely investigated membrane phosphoprotein of the nervous system (Benowitz, L.I., and A. Routtenberg. 1987. Trends Neurosci. 10:527-532; Skene, J. H. P. 1989. Annu. Rev. Neurosci. 12:127-156), with a hitherto unknown function. We have previously demonstrated that astrocytes, brain macroglial cells, contain GAP-43 (Steisslinger, H. W., V. J. Aloyo, and L. Vitković, 1987. Brain Res. 415:375-379; Vitković, L., H. W. Steisslinger, V. J. Aloyo, and M. Mersel. 1988. Proc. Natl. Acad. Sci. USA. 85:8296-8300; Vitković L., and M. Mersel. 1989. Metab. Brain Dis. 4:47-53). Results from double immunofluorescent labeling experiments presented here show that oligodendrocytes also contain GAP-43 immunoreactivity (GAP-43ir). Thus, all three macroglial cell types of the central nervous system (type I and type 2 astrocytes and oligodendrocytes) contain GAP-43. Whereas immunoreactive GAP-43 is expressed by progenitors of all macroglial cell types, the developmental regulation of its expression is cell type specific. Immunoreactive GAP-43 is downregulated in type 1 astrocytes, and constitutively expressed in both type 2 astrocytes and oligodendrocytes. These results may be relevant to potential function(s) of GAP-43.


Sign in / Sign up

Export Citation Format

Share Document