Wnt-4 is a mesenchymal signal for epithelial transformation of metanephric mesenchyme in the developing kidney

Development of the mammalian kidney is initiated by ingrowth of the ureteric bud into the metanephric blastema. In response to signal(s) from the ureter, mesenchymal cells condense, aggregate into pretubular clusters, and undergo epithelialisation to form simple epithelial tubules. Subsequent morphogenesis and differentiation of the tubular epithelium lead to the establishment of a functional nephron. Here we demonstrate that Wnt-4, a secreted glycoprotein which is required for tubule formation, is sufficient to trigger tubulogenesis in isolated metanephric mesenchyme, whereas Wnt-11 which is expressed in the tip of the growing ureter is not. Wnt-4 signaling depends on cell contact and sulphated glycosaminoglycans and is only required for triggering tubulogenesis but not for later events. The Wnt-4 signal can be replaced by other members of the Wnt gene family including Wnt-1, Wnt-3a, Wnt-7a and Wnt-7b. Further, dorsal spinal cord, which has been thought to mimic ureteric signaling in tubule induction induces Wnt-4 mutant as well as wild-type mesenchyme suggesting that spinal cord derived signal(s) most likely act by mimicking the normal mesenchymal action of Wnt-4. These results lend additional support to the notion that Wnt-4 is a key auto-regulator of the mesenchymal to epithelial transformation that underpins nephrogenesis adding another level of complexity in the hierarchy of molecular events mediating tubulogenesis.

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Murine homolog of SALL1 is essential for ureteric bud invasion in kidney development

Development ◽

10.1242/dev.128.16.3105 ◽

2001 ◽

Vol 128 (16) ◽

pp. 3105-3115 ◽

Cited By ~ 9

Author(s):

Ryuichi Nishinakamura ◽

Yuko Matsumoto ◽

Kazuki Nakao ◽

Kenji Nakamura ◽

Akira Sato ◽

...

Keyword(s):

Kidney Development ◽

Perinatal Period ◽

Homozygous Deletion ◽

Homeotic Gene ◽

Metanephric Mesenchyme ◽

Ureteric Bud ◽

Mouse Homolog ◽

Tubule Formation ◽

Murine Homolog ◽

Inductive Signal

SALL1 is a mammalian homolog of the Drosophilaregion-specific homeotic gene spalt (sal); heterozygous mutations in SALL1 in humans lead to Townes-Brocks syndrome. We have isolated a mouse homolog of SALL1 (Sall1) and found that mice deficient in Sall1 die in the perinatal period and that kidney agenesis or severe dysgenesis are present. Sall1 is expressed in the metanephric mesenchyme surrounding ureteric bud; homozygous deletion ofSall1 results in an incomplete ureteric bud outgrowth, a failure of tubule formation in the mesenchyme and an apoptosis of the mesenchyme. This phenotype is likely to be primarily caused by the absence of the inductive signal from the ureter, as the Sall1-deficient mesenchyme is competent with respect to epithelial differentiation. Sall1 is therefore essential for ureteric bud invasion, the initial key step for metanephros development.

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TGF beta 2, LIF and FGF2 cooperate to induce nephrogenesis

Development ◽

10.1242/dev.128.7.1045 ◽

2001 ◽

Vol 128 (7) ◽

pp. 1045-1057 ◽

Cited By ~ 3

Author(s):

S.Y. Plisov ◽

K. Yoshino ◽

L.F. Dove ◽

K.G. Higinbotham ◽

J.S. Rubin ◽

...

Keyword(s):

Growth Factor ◽

Transforming Growth Factor Beta ◽

Transforming Growth Factor ◽

Tgf Beta ◽

Metanephric Mesenchyme ◽

Ureteric Bud ◽

Tubule Formation ◽

Wnt Ligands ◽

Metanephric Kidney ◽

Beta 2

The metanephric kidney develops from interactions between the epithelial ureteric bud and adjacent metanephric mesenchyme, which is induced by the bud to form the epithelia of the nephron. We have found that leukemia inhibitory factor (LIF) and transforming growth factor beta 2 (TGF beta 2) are secreted by inductive rat bud cells and cooperate to enhance and accelerate renal tubule formation in uninduced rat metanephric mesenchymal explants. LIF alone or TGF beta 2 with fibroblast growth factor 2 induced numerous tubules in isolated mesenchymes over an 8 day period, while (in combination) all three caused abundant tubule formation in 72 hours. Furthermore, neutralization of Wnt ligands with antagonist-secreted Frizzled-related protein 1 abrogated these responses and combinatorial cytokine/growth factor stimulation of explants augmented nuclear activation of Tcf1/Lef1, suggesting that LIF and TGF beta 2/FGF2 cooperate to regulate nephrogenesis through a common Wnt-dependent mechanism.

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Spatial and temporal expression of cell surface molecules during nephrogenesis

AJP Renal Physiology ◽

10.1152/ajprenal.1997.272.1.f79 ◽

1997 ◽

Vol 272 (1) ◽

pp. F79-F86 ◽

Cited By ~ 2

Author(s):

M. R. Goldberg ◽

J. Barasch ◽

A. Shifteh ◽

V. D'Agati ◽

J. A. Oliver ◽

...

Keyword(s):

Kidney Development ◽

Cell Interaction ◽

Mesenchymal Cells ◽

Cell Contact ◽

Distinctive Pattern ◽

Metanephric Mesenchyme ◽

Ureteric Bud ◽

Temporal Expression ◽

Functional Effect ◽

Surface Molecules

Cell-to-cell interaction is fundamental to the development of the kidney. Ureteric bud cells, through cell contact or short-distance interactions, induce the metanephric mesenchyme to convert, to epithelia and begin the process of tubulogenesis. To identify new molecules that are involved in these processes, we generated a panel of monoclonal antibodies (MAbs) to the surface of induced mesenchymal cells taken from a day 15 rat embryonic kidney rudiment. MAbs were chosen for further study based either on a distinctive pattern of expression of their antigens or their functional effect on tubulogenesis. We identified a set of MAbs that preferentially stained the glomerular crevice, the first site for formation of the glomerular anlage. Another MAb inhibited tubulogenesis by producing widespread apoptosis in induced mesenchymal cells. This approach promises to identify new molecules that are central to kidney development.

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Faculty Opinions recommendation of Loss of inhibitory interneurons in the dorsal spinal cord and elevated itch in Bhlhb5 mutant mice.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.3692960.3469054 ◽

2010 ◽

Author(s):

Stephen Hunt ◽

Sandrine Geranton ◽

Ilona Obara

Keyword(s):

Spinal Cord ◽

Mutant Mice ◽

Inhibitory Interneurons ◽

Dorsal Spinal Cord ◽

Dorsal Spinal

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Idiopathic dorsal spinal cord herniation perforating the lamina: a case report and review of the literature

Acta Neurochirurgica ◽

10.1007/s00701-021-04804-4 ◽

2021 ◽

Author(s):

Haruki Funao ◽

Satoshi Nakamura ◽

Kenshi Daimon ◽

Norihiro Isogai ◽

Yutaka Sasao ◽

...

Keyword(s):

Spinal Cord ◽

Case Report ◽

Review Of The Literature ◽

Dorsal Spinal Cord ◽

Spinal Cord Herniation ◽

Dorsal Spinal

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Getting in touch with your senses: Mechanisms specifying sensory interneurons in the dorsal spinal cord

WIREs Mechanisms of Disease ◽

10.1002/wsbm.1520 ◽

2021 ◽

Author(s):

Sandeep Gupta ◽

Samantha J. Butler

Keyword(s):

Spinal Cord ◽

Dorsal Spinal Cord ◽

Dorsal Spinal

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Analysis of the proportion and neuronal activity of excitatory and inhibitory neurons in the rat dorsal spinal cord after peripheral nerve injury

Neuroscience Letters ◽

10.1016/j.neulet.2021.135707 ◽

2021 ◽

Vol 749 ◽

pp. 135707

Author(s):

Yasuhito Motojima ◽

Yoichi Ueta ◽

Akinori Sakai

Keyword(s):

Spinal Cord ◽

Peripheral Nerve ◽

Nerve Injury ◽

Neuronal Activity ◽

Peripheral Nerve Injury ◽

Inhibitory Neurons ◽

Dorsal Spinal Cord ◽

Dorsal Spinal

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Spinal integration of antidromic mediated cutaneous vasodilation during dorsal spinal cord stimulation in the rat

Neuroscience Letters ◽

10.1016/s0304-3940(98)00972-0 ◽

1999 ◽

Vol 260 (3) ◽

pp. 173-176 ◽

Cited By ~ 12

Author(s):

Kirk W. Barron ◽

John E. Croom ◽

Crystal A. Ray ◽

Margaret J. Chandler ◽

Robert D. Foreman

Keyword(s):

Spinal Cord ◽

Spinal Cord Stimulation ◽

Dorsal Spinal Cord ◽

Cutaneous Vasodilation ◽

Dorsal Spinal

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Forskolin and phosphodiesterase inhibitors release adenosine but inhibit morphine-evoked release of adenosine from spinal cord synaptosomes

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y91-133 ◽

1991 ◽

Vol 69 (6) ◽

pp. 877-885 ◽

Cited By ~ 4

Author(s):

D. Nicholson ◽

T. D. White ◽

J. Sawynok

Keyword(s):

Spinal Cord ◽

Cyclic Amp ◽

Phosphodiesterase Inhibitor ◽

Phosphodiesterase Inhibitors ◽

Dorsal Spinal Cord ◽

Adenosine Release ◽

Basal Release ◽

Phosphodiesterase Isoenzymes ◽

Dorsal Spinal ◽

Ventral Spinal Cord

The effects of forskolin, Ro 20-1724, rolipram, and 3-isobutyl-1-methylxanthine (IBMX) on morphine-evoked release of adenosine from dorsal spinal cord synaptosomes were evaluated to examine the potential involvement of cyclic AMP in this action of morphine. Ro 20-1724 (1–100 μM), rolipram (1–100 μM), and forskolin (1–10 μM) increased basal release of adenosine, and at 1 μM inhibited morphine-evoked release of adenosine. Release of adenosine by Ro 20-1724, rolipram, and forskolin was reduced 42–77% in the presence of α, β-methylene ADP and GMP, which inhibits ecto-5′-nucleotidase activity by 81%, indicating that this adenosine originated predominantly as nucleotide(s). Significant amounts of adenosine also were released from the ventral spinal cord by these agents. Ro 20-1724 and rolipram did not significantly alter the uptake of adenosine into synaptosomes. Although Ro 20-1724 and rolipram had only limited effects on the extrasynaptosomal conversion of added cyclic AMP to adenosine, IBMX, a phosphodiesterase inhibitor with a broader spectrum of inhibitory activity for phosphodiesterase isoenzymes, significantly inhibited the conversion of cyclic AMP to adenosine and resulted in recovery of a substantial amount of cyclic AMP. As with the non-xanthine phosphodiesterase inhibitors, IBMX increased basal release of adenosine and reduced morphine-evoked release of adenosine. Adenosine released by IBMX was reduced 70% in the presence of α, β-methylene ADP and GMP, and release from the ventral spinal cord was 61% of that from the dorsal spinal cord. Collectively, these results indicate that forskolin and phosphodiesterase inhibitors release nucleotide(s) which is (are) converted extrasynaptosomally to adenosine. For forskolin, Ro 20-1724, and rolipram, the nucleotide released could be cyclic AMP. Morphine releases adenosine per se, and forskolin and phosphodiesterase inhibitors reduce this release. The lack of increase in the action of morphine with phosphodiesterase inhibitors in particular does not support a role for stimulation of cyclic AMP production by morphine in the release of adenosine. The reduction in morphine-evoked release of adenosine by forskolin and phosphodiesterase inhibitors suggests either (a) that a reduction in cyclic levels by morphine promotes adenosine release, or (b) that cyclic AMP interferes with the release process.Key words: forskolin, Ro 20-1724, 3-isobutyl-1-methylxanthine, cyclic AMP, morphine, adenosine release, spinal cord.

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