scholarly journals Fgf-signaling is compartmentalized within the mesenchyme and controls proliferation during salamander limb development

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Sruthi Purushothaman ◽  
Ahmed Elewa ◽  
Ashley W Seifert
Keyword(s):  
Cell Proliferation ◽  
Growth Factor ◽  
Cell Survival ◽  
Fibroblast Growth Factor ◽  
Sonic Hedgehog ◽  
Limb Development ◽  
Fibroblast Growth ◽  
Fgf Signaling ◽  
Anteroposterior Patterning ◽  
Distal Cell

Although decades of studies have produced a generalized model for tetrapod limb development, urodeles deviate from anurans and amniotes in at least two key respects: their limbs exhibit preaxial skeletal differentiation and do not develop an apical ectodermal ridge (AER). Here, we investigated how Sonic hedgehog (Shh) and Fibroblast growth factor (Fgf) signaling regulate limb development in the axolotl. We found that Shh-expressing cells contributed to the most posterior digit, and that inhibiting Shh-signaling inhibited Fgf8 expression, anteroposterior patterning, and distal cell proliferation. In addition to lack of a morphological AER, we found that salamander limbs also lack a molecular AER. We found that amniote and anuran AER-specific Fgfs and their cognate receptors were expressed entirely in the mesenchyme. Broad inhibition of Fgf-signaling demonstrated that this pathway regulates cell proliferation across all three limb axes, in contrast to anurans and amniotes where Fgf-signaling regulates cell survival and proximodistal patterning.

scholarly journals Cubilin, a High Affinity Receptor for Fibroblast Growth Factor 8, Is Required for Cell Survival in the Developing Vertebrate Head

2013 ◽  
Vol 288 (23) ◽  
pp. 16655-16670 ◽  
Author(s):  
Olivier Cases ◽  
Aitana Perea-Gomez ◽  
Diego P. Aguiar ◽  
Anders Nykjaer ◽  
Sabine Amsellem ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cell Survival ◽  
Fibroblast Growth Factor ◽  
Cell Uptake ◽  
Fibroblast Growth ◽  
Fgf Signaling ◽  
Mouse Development ◽  
Fibroblast Growth Factor 8 ◽  
High Affinity ◽  
Head Surface

Cubilin (Cubn) is a multiligand endocytic receptor critical for the intestinal absorption of vitamin B12 and renal protein reabsorption. During mouse development, Cubn is expressed in both embryonic and extra-embryonic tissues, and Cubn gene inactivation results in early embryo lethality most likely due to the impairment of the function of extra-embryonic Cubn. Here, we focus on the developmental role of Cubn expressed in the embryonic head. We report that Cubn is a novel, interspecies-conserved Fgf receptor. Epiblast-specific inactivation of Cubn in the mouse embryo as well as Cubn silencing in the anterior head of frog or the cephalic neural crest of chick embryos show that Cubn is required during early somite stages to convey survival signals in the developing vertebrate head. Surface plasmon resonance analysis reveals that fibroblast growth factor 8 (Fgf8), a key mediator of cell survival, migration, proliferation, and patterning in the developing head, is a high affinity ligand for Cubn. Cell uptake studies show that binding to Cubn is necessary for the phosphorylation of the Fgf signaling mediators MAPK and Smad1. Although Cubn may not form stable ternary complexes with Fgf receptors (FgfRs), it acts together with and/or is necessary for optimal FgfR activity. We propose that plasma membrane binding of Fgf8, and most likely of the Fgf8 family members Fgf17 and Fgf18, to Cubn improves Fgf ligand endocytosis and availability to FgfRs, thus modulating Fgf signaling activity.

scholarly journals Polydactylous limbs in Strong's Luxoid mice result from ectopic polarizing activity

Development ◽  
1995 ◽  
Vol 121 (7) ◽  
pp. 1971-1978 ◽  
Author(s):  
D.C. Chan ◽  
E. Laufer ◽  
C. Tabin ◽  
P. Leder
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Gene Product ◽  
Sonic Hedgehog ◽  
Limb Development ◽  
Axis Formation ◽  
Fibroblast Growth ◽  
Normal Pattern ◽  
Anterior Side ◽  
Genetically Determined

Strong's Luxoid (1stD) is a semidominant mouse mutation in which heterozygotes show preaxial hindlimb polydactyly, and homozygotes show fore- and hindlimb polydactyly. The digit patterns of these polydactylous limbs resemble those caused by polarizing grafts, since additional digits with posterior character are present at the anterior side of the limb. Such observations suggest that 1stD limb buds might contain a genetically determined ectopic region of polarizing activity. Accordingly, we show that mutant embryos ectopically express the pattern-determining genes fibroblast growth factor 4 (fgf-4), sonic hedgehog (shh), and Hoxd-12 in the anterior region of the limb. Further, we show that anterior mesoderm from mutant limbs exhibits polarizing activity when grafted into host chicken limbs. In contrast to an experimentally derived polydactylous transgenic mouse, forelimbs of homozygotes show a normal pattern of Hoxb-8 expression, indicating that the duplication of polarizing tissue here occurs downstream or independently of Hoxb-8. We suggest that the 1st gene product is involved in anteroposterior axis formation during normal limb development.

Basic fibroblast growth factor promotes subplate cell survival in explant cultures of embryonic mouse cortex

1999 ◽  
Vol 271 (3) ◽  
pp. 143-146 ◽  
Author(s):  
Stephen Cooke ◽  
Grace Grant ◽  
Clare McLauchlan ◽  
R.Beau Lotto ◽  
David J. Price
Keyword(s):  
Growth Factor ◽  
Cell Survival ◽  
Fibroblast Growth Factor ◽  
Basic Fibroblast Growth Factor ◽  
Fibroblast Growth ◽  
Embryonic Mouse ◽  
Mouse Cortex ◽  
Explant Cultures

Bio-orthogonal Immobilization of Fibroblast Growth Factor 2 for Spatial Controlled Cell Proliferation

2015 ◽  
Vol 1 (9) ◽  
pp. 740-746 ◽  
Author(s):  
Tessa Lühmann ◽  
Gabriel Jones ◽  
Marcus Gutmann ◽  
Jens-Christoph Rybak ◽  
Joachim Nickel ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 2 ◽  
Fibroblast Growth
Sign in / Sign up

Export Citation Format

Share Document