Developmental Localization of the Splicing Alternatives of Fibroblast Growth Factor Receptor-2 (FGFR2)

Orr-Urtreger, Avi; Bedford, Mark T.; Burakova, Tatjana; Arman, Esther; Zimmer, Yitzhak; Yayon, Avner; Givol, David; Lonai, Peter

doi:10.1006/dbio.1993.1205

Cited by 533 publications

(375 citation statements)

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“…Receptors capable of ditional new sites of both KGF and KGFR synthesis binding FGF family members have been detected in (see Tables 1 and 2). In addition, we have noted the somites and/or muscular derivatives (Stark et al, 1991;presence of considerable variation in KGF and KGFR Peters et al, 1992;Orr-Urtreger et al, 1993). However, expression in organs of the abdominal cavity, which given the overlapping binding specificity of many FGF were not reported by the previous studies.…”

Section: Discussionmentioning

confidence: 81%

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Pattern of keratinocyte growth factor and keratinocyte growth factor receptor expression during mouse fetal development suggests a role in mediating morphogenetic mesenchymal‐epithelial interactions

Finch

Cunha

Rubin

et al. 1995

Developmental Dynamics

266

172

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Mesenchymal cells are required for the induction of epithelial development during mammalian organogenesis. Keratinocyte growth factor (KGF) is a mesenchymally derived mitogen with specific activity for epithelial cells, suggesting that it may play a role in mediating these interactions. To further evaluate this hypothesis, in situ hybridization was used to examine the spatial distribution of KGF and KGF receptor (KGFR) transcripts during organogenesis and limb formation in mouse embryos (days 14.5 through 16.5). To facilitate this aim, mouse KGF cDNA clones were isolated. There was extensive identity between the deduced mouse KGF protein sequence and that of its human and rat cognates, indicating that this gene has been highly conserved during mammalian evolution. In addition, mouse KGF protein was purified from fibroblasts and demonstrated to be structurally and functionally similar to human KGF protein. For organs within the integumental, respiratory, gastrointestinal, and urogenital systems, whose development is dependent upon mesenchymal‐epithelial interactions, KGF mRNA was detected in mesenchymal cells, while epithelial cells expressed transcripts for the KGFR. KGF and KGFR mRNA was also expressed in certain other tissues such as perichondrium, cartilage of developing bones, developing skeletal muscle, and visceral smooth muscle whose development is not regulated by mesenchymal‐epithelial interactions. KGF expression was also detected in tissues isolated from human embryos, suggesting similar functions for KGF in human development. Taken together, our results suggest that KGF plays an important role in mediating mesenchymal‐epithelial interactions during organogenesis, but may also have other developmental functions in tissues not governed by such interactions. ©1995 Wiley‐Liss, Inc.

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Section: Discussionmentioning

confidence: 81%

“…Orr-Urtreger et al (1993). Col. duct = collecting ducts; Epi = epithelium; ND = not determined; NR = not reported; Sm.…”

Section: Kgf Kgfrmentioning

confidence: 98%

Pattern of keratinocyte growth factor and keratinocyte growth factor receptor expression during mouse fetal development suggests a role in mediating morphogenetic mesenchymal‐epithelial interactions

Finch

Cunha

Rubin

et al. 1995

Developmental Dynamics

266

172

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“…In the case of ®broblast growth factor receptor type 2, for example, alternative exon usage in the immunoglobulin-like loop region results in receptor variants with di erent ligand-binding a nities (Miki et al, 1992;Yayon et al, 1992). These transcripts are expressed in a tissue-and developmental stage-speci®c fashion (Orr-Urtreger et al, 1993;McDonald, 1994;Shi et al, 1994). The relatively high expression of RET2/6 in early human renal development may suggest a requirement for this speci®c RET isoform during that time.…”

Section: Discussionmentioning

confidence: 99%

The expression of RET and its multiple splice forms in developing human kidney

et al. 1997

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A series of inductive events between two di erent cell groups, the ureteric bud epithelium and metanephric mesenchyme, gives rise to the functional mammalian kidney. These reciprocal inductive interactions involve a number of molecules, one of which is the RET receptor tyrosine kinase. The phenotype of mice lacking functional RET includes kidney agenesis or severe dysgenesis, indicating a requirement for RET in kidney organogenesis. To investigate RET expression in human kidney development, we used a semi-quantitative RT ± PCR-based strategy to examine a panel of kidney RNA samples ranging from 8 ± 24 weeks gestational age. We found RET expression was highest earlier in development (14 weeks) with expression decreasing through to 24 weeks gestation. While three alternative RET transcripts generated by exon skipping at the 5' end of the gene were all detected throughout kidney development, expression of one transcript, RET2/6, where exon 2 was spliced to exon 6, varied relative to full length RET during this period. Levels of RET2/6 were highest at the earliest age of fetal kidney examined (8 weeks) and decreased relative to all other RET transcripts to low adult levels. The period of high expression coincides with a period of rapid bud bifurcation. Thus, it is possible that RET2/6 has a role in the early growth and di erentiation of the human kidney.

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“…We showed previously that FGFR2 is expressed in the basal layer of cells in the wound epithelium as well as in the core of the blastema adjacent to and surrounding the bisected bone during the stages of regeneration associated with growth and blastema cell proliferation (Poulin et al, 1993). Since the wound epithelium originates from the skin epidermis and KGFR has been shown to be expressed in the epidermis in early development (Orr-Urtreger et al, 1993;Shi et al, 1994), it was of interest to establish if KGFR variant expression would be responsible for the wound epithelial expression observed using the general FGFR2 probe. In fact, the KGFR variant is expressed in the wound epithe-382 POULIN AND CHIU bone ( Fig.…”

Section: Discussionmentioning

confidence: 99%

Re‐programming of expression of the KGFR and bek variants of fibroblast growth factor receptor 2 during limb regeneration in newts (Notophthalmus viridescens)

Poulin

Chiu

1995

Developmental Dynamics

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We have previously shown, by in situ hybridization, that fibroblast growth factor receptor 2 (FGFRB) is present in the basal layer of wound epithelium during limb regeneration in newts (Notophthalmus viridescens). In contrast, FGFRl expression is observed throughout the blastema mesenchyme but is distinctly absent from the wound epithelium (Poulin et al. [1993] Development 1193534361). Sequence analysis revealed that we have isolated both the KGFR and bek variants of FGFR2. These two variants differ only in the second half of the last of their three (or two) Ig-like domains. In this report, we show the expression patterns of FGFRB variants during limb regeneration by in situ hybridization. During the pre-blastema stages of regeneration, FGFRB expression was observed in the basal layer of the wound epithelium and in the cells of the periosbum. The wound epithelial hybridization was observed when the KGFR-specific probe was used while the bek-specific probe hybridized to mRNA in the cells of the periosteum. As regeneration progresses to the blastema stages, KGFR expression continued to be observed in the basal layer of the wound epithelium with additional hybridization seen in the blastema mesenchyme closely associated with the bisected bones. The bek-specific hybridization pattern observed at this stage corresponds specifically to the mesenchymal hybridization. In the differentiation stages of regeneration, the mesenchymal expression of FGFR2 becomes restricted to the cells of the condensing cartilage and later to the perichondrium. Interestingly, there appears to be a dorsoventral gradient of the expression of both KGFR and bek variants of FGFR2, which are opposite each other at the later stages of regeneration. Thus, re-programming of expression of the two FGFR2 variants is required during the initial wound closure of limb regeneration. Remarkably, the expression patterns of KGFR and bek mimic those observed in the mouse limb bud during early embryonic development (Orr-Urtreger et al. [1993]

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Developmental Localization of the Splicing Alternatives of Fibroblast Growth Factor Receptor-2 (FGFR2)

Cited by 533 publications

References 0 publications

Pattern of keratinocyte growth factor and keratinocyte growth factor receptor expression during mouse fetal development suggests a role in mediating morphogenetic mesenchymal‐epithelial interactions

Pattern of keratinocyte growth factor and keratinocyte growth factor receptor expression during mouse fetal development suggests a role in mediating morphogenetic mesenchymal‐epithelial interactions

The expression of RET and its multiple splice forms in developing human kidney

Re‐programming of expression of the KGFR and bek variants of fibroblast growth factor receptor 2 during limb regeneration in newts (Notophthalmus viridescens)

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