Hindbrain patterning: FGFs regulate Krox20 and mafB/kr expression in the otic/preotic region

Development ◽  
2000 ◽  
Vol 127 (22) ◽  
pp. 4925-4935 ◽  
Author(s):  
F. Marin ◽  
P. Charnay

Krox20 and mafB/kr are regulatory genes involved in hindbrain segmentation and anteroposterior (AP) patterning. They are expressed in rhombomeres (r) r3/r5 and r5/r6 respectively, as well as in the r5/r6 neural crest. Since several members of the fibroblast growth factor (FGF) family are expressed in the otic/preotic region (r2-r6), we investigated their possible involvement in the regulation of Krox20 and mafB/kr. Application of exogenous FGFs to the neural tube of 4- to 7-somite chick embryos led to ectopic expression in the neural crest of the somitic hindbrain (r7 and r8) and to the extension of the Krox20- or mafB/kr-positive areas in the neuroepithelium. Application of an inhibitor of FGF signalling led to severe and specific downregulation of Krox20 and mafB/kr in the hindbrain neuroepithelium and neural crest. These data indicate that FGFs are involved in the control of regional induction and/or maintenance of Krox20 and mafB/kr expression, thus identifying a novel function for these factors in hindbrain development, besides their proposed more general role in early neural caudalisation.

Development ◽  
1998 ◽  
Vol 125 (1) ◽  
pp. 51-60 ◽  
Author(s):  
H. Ohuchi ◽  
J. Takeuchi ◽  
H. Yoshioka ◽  
Y. Ishimaru ◽  
K. Ogura ◽  
...  

It has been reported that members of the fibroblast growth factor (FGF) family can induce additional limb formation in the flank of chick embryos. The phenotype of the ectopic limb depends on the somite level at which it forms: limbs in the anterior flank resemble wings, whereas those in the posterior flank resemble legs. Ectopic limbs located in the mid-flank appear chimeric, possessing characteristics of both wings and legs; feather buds are present in the anterior halves with scales and claws in the posterior halves. To study the mechanisms underlying the chimerism of these additional limbs, we cloned chick Tbx5 and Tbx4 to use as forelimb and hindlimb markers and examined their expression patterns in FGF-induced limb buds. We found that Tbx5 and Tbx4 were differentially expressed in the anterior and posterior halves of additional limb buds in the mid-flank, respectively, consistent with the chimeric patterns of the integument. A boundary of Tbx5/Tbx4 exists in all ectopic limbs, indicating that the additional limbs are essentially chimeric, although the degree of chimerism is dependent on the position. The boundary of Tbx5/Tbx4 expression is not fixed at a specific position within the interlimb region, but dependent upon where FGF was applied. Since the ectopic expression patterns of Tbx5/Tbx4 in the additional limbs are closely correlated with the patterns of their chimeric phenotypes, it is likely that Tbx5 and Tbx4 expression in the limb bud is involved in determination of the forelimb and hindlimb identities, respectively, in vertebrates.


Development ◽  
1993 ◽  
Vol 119 (4) ◽  
pp. 1067-1078 ◽  
Author(s):  
M. Kengaku ◽  
H. Okamoto

The vertebrate nervous system is initially induced from a section of dorsal ectoderm by signal(s) from the underlying dorsal mesoderm during gastrulation. In an effort to identify the neural inducing factor(s) emanating from the dorsal mesoderm, we have examined the inductive action of various growth factors by applying them to ectoderm cells from Xenopus gastrulae (8- to 12.5-hour age; embryonic stage 9+ to 11 1/2) in a microculture system. Monoclonal antibodies that specifically recognize cellular differentiation antigens from three distinct ectoderm lineages (N1 for CNS neurons from neural tube, Me1 for melanophores from neural crest and E3 for skin epidermal cells from epidermal lineages, respectively) and a mesoderm lineage (Mu1 for muscle cells) were used as markers to monitor the differentiation of cultured ectoderm cells. We found that basic fibroblast growth factor (bFGF) was capable of specifically and reproducibly inducing gastrula ectoderm cells to produce CNS neurons and melanophores at concentrations as low as 5 pM, a value about 50-fold lower than that required to induce the formation of muscle cells from blastula animal cap cells (6-hour age; stage 8+). The induction of neural lineages by bFGF was correlated with a suppression of epidermal differentiation in a dose-dependent manner. bFGF never induced the formation of muscle cells from gastrula ectoderm cells even at concentrations as high as 5 nM. The response of ectoderm cells to bFGF changed dramatically during gastrulation. Ectoderm cells from early (8- to 9-hour age; stage 9+ to 10) gastrula gave rise to CNS neurons, but yielded few melanophores. As ectoderm cells were prepared from gastrulae of increasing age, their competence to form neurons was gradually lost, whereas the production of melanophores was enhanced and peaked in 11-hour gastrula (stage 10 1/2). The ability to form both neurons and melanophores was substantially reduced in 12.5-hour gastrula (stage 11 1/2). By examining ectoderm cells from the ventral and dorsal sides independently, it was also shown that during gastrulation the change in response to bFGF of the ventral ectoderm preceded that of the dorsal ectoderm. The state of competence of the ectoderm changed primarily due to intrinsic factors rather than by instruction from other parts of the gastrula embryo. This was shown by adding bFGF to cultures of ectoderm cells that were isolated at 9-hour (stage 10) and cultured for increasing periods to allow their autonomous development. The time course of both loss of neuronal competence and gain and loss of melanophore competence closely paralleled that observed in vivo during gastrulation.(ABSTRACT TRUNCATED AT 400 WORDS)


Development ◽  
1992 ◽  
Vol 115 (4) ◽  
pp. 1059-1069 ◽  
Author(s):  
G. Brill ◽  
N. Vaisman ◽  
G. Neufeld ◽  
C. Kalcheim

We present evidence that basic fibroblast growth factor (bFGF)-producing cells stimulate primary differentiation of neurons from neural crest progenitors. Baby hamster kidney (BHK-21) cells were stably cotransfected with plasmid pSV2/neo, which contains the gene conferring resistance to the neomycin analog G418 and expression vectors containing the human bFGF cDNA. Various clones, which differed in their bFGF production levels, were isolated. Homogeneous neural crest cells were cultured on monolayers of bFGF-producing, BHK-21-derived cell lines. While the parental BHK-21 cells, which do not produce detectable bFGF, had poor neurogenic ability, the various bFGF-producing clones promoted a 1.5- to 4-fold increase in neuronal cell number compared to the parental cells. This increase was correlated with the levels of bFGF produced by the different transfected clones, which ranged between 2.3 and 140 ng/mg protein. In contrast, no stimulation of neuronal differentiation was observed when neural crest cells were grown on monolayers of parental BHK cells transfected with plasmid pSV2/neo alone, or on a parental BHK-derived clone, which secretes high amounts of recombinant vascular endothelial growth factor (VEGF). Furthermore, the neuron-promoting ability of bFGF-producing cells could be mimicked by addition of exogenous bFGF to neural crest cells grown on the parental BHK line. A similar treatment of neural crest cells grown on laminin substrata, instead of BHK cells, resulted in increased survival of non-neuronal cells, but not of neurons (see also Kalcheim, C. 1989, Dev. Biol. 134, 1–10). Taken together, these results suggest that bFGF stimulates neuronal differentiation of neural crest cells by a cell-mediated signalling mechanism.


1994 ◽  
Vol 14 (6) ◽  
pp. 4244-4250
Author(s):  
J C Fox ◽  
A Y Hsu ◽  
J L Swain

Acidic fibroblast growth factor (FGF) and related family members regulate differentiation in organisms as diverse as Xenopus laevis and mammals. We utilized a well-characterized model of myogenic development to directly assess the importance of endogenously produced FGF in controlling differentiation. A role for endogenous FGF is suggested by the previous finding that acidic and basic FGF abundance in cultured myocytes decreases during differentiation. In this study we inhibited the endogenous production of FGF in murine Sol 8 myoblasts by using antisense RNA and observed precocious myogenic differentiation. Exogenously supplied acidic FGF rescues this phenotype. Further results suggest that the effect of FGF on myogenic differentiation is mediated in part through inhibition of myogenin expression. These results demonstrate a direct role for endogenously synthesized growth factors in regulating myogenesis and provide support for a general role for related proteins in mammalian development.


2002 ◽  
Vol 224 (2) ◽  
pp. 210-221 ◽  
Author(s):  
Anita Petiot ◽  
Patrizia Ferretti ◽  
Andrew J. Copp ◽  
Chi-Tsung Joseph Chan

1994 ◽  
Vol 14 (6) ◽  
pp. 4244-4250 ◽  
Author(s):  
J C Fox ◽  
A Y Hsu ◽  
J L Swain

Acidic fibroblast growth factor (FGF) and related family members regulate differentiation in organisms as diverse as Xenopus laevis and mammals. We utilized a well-characterized model of myogenic development to directly assess the importance of endogenously produced FGF in controlling differentiation. A role for endogenous FGF is suggested by the previous finding that acidic and basic FGF abundance in cultured myocytes decreases during differentiation. In this study we inhibited the endogenous production of FGF in murine Sol 8 myoblasts by using antisense RNA and observed precocious myogenic differentiation. Exogenously supplied acidic FGF rescues this phenotype. Further results suggest that the effect of FGF on myogenic differentiation is mediated in part through inhibition of myogenin expression. These results demonstrate a direct role for endogenously synthesized growth factors in regulating myogenesis and provide support for a general role for related proteins in mammalian development.


2021 ◽  
Vol 12 ◽  
Author(s):  
Hui Sun ◽  
Matthew Sherrier ◽  
Hongshuai Li

Fibroblast growth factor 21 (FGF21) is an atypical member of the FGF family, which functions as a powerful endocrine and paracrine regulator of glucose and lipid metabolism. In addition to liver and adipose tissue, recent studies have shown that FGF21 can also be produced in skeletal muscle. As the most abundant tissue in the human body, skeletal muscle has become increasingly recognized as a major site of metabolic activity and an important modulator of systemic metabolic homeostasis. The function and mechanism of action of muscle-derived FGF21 have recently gained attention due to the findings of considerably increased expression and secretion of FGF21 from skeletal muscle under certain pathological conditions. Recent reports regarding the ectopic expression of FGF21 from skeletal muscle and its potential effects on the musculoskeletal system unfolds a new chapter in the story of FGF21. In this review, we summarize the current knowledge base of muscle-derived FGF21 and the possible functions of FGF21 on homeostasis of the musculoskeletal system with a focus on skeletal muscle and bone.


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