Retinoic Acid Gradients during Limb Regeneration

Scadding, Steven R.; Maden, Malcolm

doi:10.1006/dbio.1994.1114

Cited by 90 publications

(52 citation statements)

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“…We report here that both atRA and 9-cis-RA are present in the molluscan CNS (and hemolymph) in nM concentrations, although the concentration of atRA was estimated to be slightly higher than 9-cis-RA. The estimated concentrations reported in this study are in accordance with previous detection levels of RA in vertebrate limb tissue (Thaller and Eichele, 1987;Scadding and Maden, 1994) as well as locust embryo (Nowickyj, 2008). Interestingly, in the locust embryo, 9-cis-RA was slightly more abundant than atRA (Nowickyj et al, 2008).…”

Section: Discussionsupporting

confidence: 91%

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Detection of Endogenous Retinoids in the Molluscan CNS and Characterization of the Trophic and Tropic Actions of 9-cisRetinoic Acid on Isolated Neurons

Dmetrichuk

Carlone²,

Jones³

et al. 2008

J. Neurosci.

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Retinoic acid (RA) is an active metabolite of Vitamin A that plays an important role in the growth and differentiation of many cell types. All-trans RA (atRA) is the retinoic acid isomer that has been most widely studied in the nervous system, and can induce and direct neurite outgrowth from both vertebrate and invertebrate preparations. The presence and role of the 9-cis-RA isomer in the nervous system is far less well defined. Here, we used high-pressure liquid chromatography (HPLC) and mass spectrometry (MS) to show for the first time, the presence of both atRA and 9-cis-RA in the CNS of an invertebrate. We then demonstrated that 9-cis-RA was capable of exerting the same neurotrophic and chemotropic effects on cultured neurons as atRA. In this study, significantly more cells showed neurite outgrowth in 9-cis-RA versus the EtOH vehicle control, and 9-cis-RA significantly increased the number and length of neurites from identified neurons after 4 d in culture. 9-cis-RA also extended the duration of time that cells remained electrically excitable in culture. Furthermore, we showed for the first time in any species, that exogenous application of 9-cis-RA induced positive growth cone turning of cultured neurons. This study provides the first evidence for the presence of both atRA and 9-cis-RA in an invertebrate CNS and also provides the first direct evidence for a potential physiological role for 9-cis-RA in neuronal regeneration and axon pathfinding.

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Section: Discussionsupporting

confidence: 91%

“…From this analysis, with an estimated RA extraction efficiency of 70% (Scadding and Maden, 1994), we calculated endogenous atRA concentration in the CNS tissue to be 77.14 pg/mg wet weight (693 nM), while in the hemolymph, the concentration was estimated at 17.22 pg/mg wet weight (155 nM) (Fig. 5).…”

Section: Estimation Of Endogenous Retinoid Levelsmentioning

confidence: 99%

Detection of Endogenous Retinoids in the Molluscan CNS and Characterization of the Trophic and Tropic Actions of 9-cisRetinoic Acid on Isolated Neurons

Dmetrichuk

Carlone²,

Jones³

et al. 2008

J. Neurosci.

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“…This idea is supported by several lines of evidence. First, RA is present in posterior–anterior and distal to proximal gradients within the blastema, which is what might be expected given that RA proximalizes distal blastema cells (Scadding & Maden, 1994) and simultaneously posteriorizes them (see later). Second, CRABP levels are significantly higher in the blastemas of RA‐treated limbs (Keeble & Maden, 1986).…”

Section: Pattern Formation In the Blastemamentioning

confidence: 70%

Mechanisms of urodele limb regeneration

Stocum

2017

Regeneration

109

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This review explores the historical and current state of our knowledge about urodele limb regeneration. Topics discussed are (1) blastema formation by the proteolytic histolysis of limb tissues to release resident stem cells and mononucleate cells that undergo dedifferentiation, cell cycle entry and accumulation under the apical epidermal cap. (2) The origin, phenotypic memory, and positional memory of blastema cells. (3) The role played by macrophages in the early events of regeneration. (4) The role of neural and AEC factors and interaction between blastema cells in mitosis and distalization. (5) Models of pattern formation based on the results of axial reversal experiments, experiments on the regeneration of half and double half limbs, and experiments using retinoic acid to alter positional identity of blastema cells. (6) Possible mechanisms of distalization during normal and intercalary regeneration. (7) Is pattern formation is a self‐organizing property of the blastema or dictated by chemical signals from adjacent tissues? (8) What is the future for regenerating a human limb?

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“…We also compared the gradient with another likely morphogen (although one which is not GJC-related): retinoic acid. Gradients of retinoic acid have been measured between 2.5-and 2.7-fold in the anterior vs. posterior side of the developing limb and proximal vs. distal cells in the regenerating limb blastema (Eichele and Thaller, 1987;Scadding and Maden, 1994). Protein morphogens such as activin can induce different gene expression levels at receptor occupancy levels that differ by approximately 3 to 1 Gurdon et al, 1998Gurdon et al, , 1999Shimizu and Gurdon, 1999).…”

Section: Comparison To Other Morphogen Gradientsmentioning

confidence: 99%

Mathematical model of morphogen electrophoresis through gap junctions

Esser

Smith

Weaver

et al. 2006

Developmental Dynamics

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Gap junctional communication is important for embryonic morphogenesis. However, the factors regulating the spatial properties of small molecule signal flows through gap junctions remain poorly understood. Recent data on gap junctions, ion transporters, and serotonin during left-right patterning suggest a specific model: the net unidirectional transfer of small molecules through long-range gap junctional paths driven by an electrophoretic mechanism. However, this concept has only been discussed qualitatively, and it is not known whether such a mechanism can actually establish a gradient within physiological constraints. We review the existing functional data and develop a mathematical model of the flow of serotonin through the early Xenopus embryo under an electrophoretic force generated by ion pumps. Through computer simulation of this process using realistic parameters, we explored quantitatively the dynamics of morphogen movement through gap junctions, confirming the plausibility of the proposed electrophoretic mechanism, which generates a considerable gradient in the available time frame. The model made several testable predictions and revealed properties of robustness, cellular gradients of serotonin, and the dependence of the gradient on several developmental constants. This work quantitatively supports the plausibility of electrophoretic control of morphogen movement through gap junctions during early left-right patterning. This conceptual framework for modeling gap junctional signaling-an epigenetic patterning mechanism of wide relevance in biological regulation-suggests numerous experimental approaches in other patterning systems.

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Retinoic Acid Gradients during Limb Regeneration

Cited by 90 publications

References 0 publications

Detection of Endogenous Retinoids in the Molluscan CNS and Characterization of the Trophic and Tropic Actions of 9-cisRetinoic Acid on Isolated Neurons

Detection of Endogenous Retinoids in the Molluscan CNS and Characterization of the Trophic and Tropic Actions of 9-cisRetinoic Acid on Isolated Neurons

Mechanisms of urodele limb regeneration

Mathematical model of morphogen electrophoresis through gap junctions

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