Distinct expression patterns of insulin-like growth factor binding proteins 2 and 5 during fetal and postnatal development.

Green, Barrett N.; Jones, Stephanie B.; Streck, Randal D.; Wood, Teresa L.; Rotwein, Peter; Pintar, John E.

doi:10.1210/endo.134.2.7507840

Cited by 91 publications

(47 citation statements)

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“…It belongs to a family of secreted proteins that bind IGF1 and 2, thereby modulating their biological actions. It is known to be expressed in embryogenesis during muscle development (32) and is rapidly induced during terminal muscle differentiation of C2l myoblasts coincident with the onset of Myogenin gene expression (33). Indeed, we found that PF-1, the clone that expressed the highest level of Myogenin, also showed high levels of Igfbp5.…”

Section: Induction Of a Myogenic Transcription Program By Pax3-fkhrmentioning

confidence: 58%

cDNA microarrays detect activation of a myogenic transcription program by the PAX3-FKHR fusion oncogene

et al. 1999

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Alveolar rhabdomyosarcoma is an aggressive pediatric cancer of striated muscle characterized in 60% of cases by a t(2;13)(q35;q14). This results in the fusion of PAX3, a developmental transcription factor required for limb myogenesis, with FKHR, a member of the forkhead family of transcription factors. The resultant PAX3-FKHR gene possesses transforming properties; however, the effects of this chimeric oncogene on gene expression are largely unknown. To investigate the actions of these transcription factors, both Pax3 and PAX3-FKHR were introduced into NIH 3T3 cells, and the resultant gene expression changes were analyzed with a murine cDNA microarray containing 2,225 elements. We found that PAX3-FKHR but not PAX3 activated a myogenic transcription program including the induction of transcription factors MyoD, Myogenin, Six1, and Slug as well as a battery of genes involved in several aspects of muscle function. Notable among this group were the growth factor gene Igf2 and its binding protein Igfbp5. Relevance of this model was suggested by verification that three of these genes (IGFBP5, HSIX1, and Slug) were also expressed in alveolar rhabdomyosarcoma cell lines. This study utilizes cDNA microarrays to elucidate the pattern of gene expression induced by an oncogenic transcription factor and demonstrates the profound myogenic properties of PAX3-FKHR in NIH 3T3 cells.

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Section: Induction Of a Myogenic Transcription Program By Pax3-fkhrmentioning

confidence: 58%

cDNA microarrays detect activation of a myogenic transcription program by the PAX3-FKHR fusion oncogene

et al. 1999

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“…IGF-I can stimulate the proliferation of dissociated limb mesenchymal cells (Kaplowitz et al, 1982) and explanted limb buds Bhaumick and Bala, 1987), suggesting that IGF-I might be involved in promoting the proliferation and outgrowth of limb mesoderm in response to the AER. In addition, IGF peptides and IGF-I receptors are present in the AER itself (Ralphs et al, 1990;, and IGF binding protein-2 (IGFBP-2) and IGF binding protein-5 (IGFBP-5), which can modulate the activity of IGF-I, are expressed by the AER of the rat limb bud (Streck et al, 1992;Green et al, 1994), suggesting the possibility that IGF-I may be involved in some aspect of AER activity. Insulin is also present in the chick and mouse embryo during early stages of limb development (De Pablo et al, 1982;Spaventi et al, 1990;Deltour et al, 19931, and specific insulin receptors are present in the chick limb bud during its outgrowth (Bassas et al, 1988), although their spatial distribution has not been determined.…”

Section: Introductionmentioning

confidence: 99%

Studies on insulin‐like growth factor‐I and insulin in chick limb morphogenesis

Dealy

Kosher

1995

Developmental Dynamics

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The apical ectodermal ridge (AER) promotes the proliferation and directed outgrowth of the subridge mesodermal cells of the developing limb bud, while suppressing their differentiation. Insulin-like growth factor-I (IGF-I) and its receptor are expressed by the subridge mesodermal cells of the chick limb bud growing out in response to the AER, and specific insulin receptors are present in the limb bud during its outgrowth. To study the possible roles of IGF-I and insulin in limb outgrowth, we have examined their effects on the morphogenesis of posterior and anterior portions of the distal tip of stage 25 embryonic chick wing buds subjected to organ culture in serum-free medium in the presence or absence of the AER and limb ectoderm. The distal mesoderm of control posterior explants lacking an AER or all limb ectoderm ceases expressing IGF-I mRNA, exhibits little or no proliferation, fails to undergo outgrowth, and rapidly differentiates. Exogenous IGF-I and insulin promote the outgrowth and proliferation and suppress the differentiation of distal mesodermal cells in posterior explants lacking an AER or limb ectoderm, thus mimicking at least to some extent the outgrowth promoting and antidifferentiative effects normally elicited on the subridge mesoderm by the AER. Furthermore, IGF-I and insulin-treated posterior explants exhibit high IGF-I mRNA expression, indicating that IGF-I and insulin maintain the expression of endogenous IGF-I by the subridge mesoderm. We have also found IGF-I and insulin can affect the morphology and activity of the AER. When the posterior portion of the wing bud tip is cultured with the AER intact in control medium, on day 4-5 the AER flattens, ceases expressing high amounts of the AER-characteristic homeobox-containing gene MsxZ, and concomitantly an elongated cartilaginous element differentiates in the subridge mesoderm. In contrast, in the presence of exogenous IGF-I or insulin the AER of such explants does not flatten, continues expressing high amounts of MsxZ, and the subridge mesoderm remains undifferentiated and proliferative. Thus, exogenous IGF-I and insulin maintain the thickness of the AER and sustain its expression of Msx2, while sustaining the anti-differentiative effect normally elicited on the subridge mesoderm by a thickened functional AER. Notably, we have 0 1995 WILEY-LISS, INC. also found that exogenous IGF-I and insulin induce the formation of a thickened ridge-like structure that expresses high amounts of Msx2 from the normally thin distal anterior ectoderm of the limb bud, while promoting dramatic outgrowth and proliferation of the anterior mesoderm, which normally undergoes little outgrowth or proliferation. These studies provide support for the hypothesis that endogenous IGF-I and insulin may be involved in promoting the outgrowth and suppressing the differentiation of limb mesoderm in response to the AER, and also in regulating and/or maintaining at least some aspects of AER activity.0 1995 Wiley-Liss, Inc.

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“…In mice, Igfbp5 is expressed in the embryo from early development, principally in the myotomal component of the somites and developing central nervous system (8). Postnatally, serum IGFBP-5, in common with IGFBP-3, forms a ternary complex with IGF-I or IGF-II and the acid-labile subunit (9).…”

mentioning

confidence: 99%

Insulin-like growth factor-binding protein 5 ( Igfbp5 ) compromises survival, growth, muscle development, and fertility in mice

Salih

Tripathi

Holding

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

160

123

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The insulin-like growth factors (IGFs) are essential for development; bioavailable IGF is tightly regulated by six related IGF-binding proteins (IGFBPs). Igfbp5 is the most conserved and is developmentally up-regulated in key lineages and pathologies; in vitro studies suggest that IGFBP-5 functions independently of IGF interaction. Genetic ablation of individual Igfbps has yielded limited phenotypes because of substantial compensation by remaining family members. Therefore, to reveal Igfbp5 actions in vivo, we generated lines of transgenic mice that ubiquitously overexpressed Igfbp5 from early development. Significantly increased neonatal mortality, reduced female fertility, whole-body growth inhibition, and retarded muscle development were observed in Igfbp5-overexpressing mice. The magnitude of the response in individual transgenic lines was positively correlated with Igfbp5 expression. Circulating IGFBP-5 concentrations increased a maximum of only 4-fold, total and free IGF-I concentrations increased up to 2-fold, and IGFBP-5 was detected in high Mr complexes; however, no detectable decrease in the proportion of free IGF-I was observed. Thus, despite only modest changes in IGF and IGFBP concentrations, the Igfbp5-overexpressing mice displayed a phenotype more extreme than that observed for other Igfbp genetic models. Although growth retardation was obvious prenatally, maximal inhibition occurred postnatally before the onset of growth hormone-dependent growth, regardless of Igfbp5 expression level, revealing a period of sensitivity to IGFBP-5 during this important stage of tissue programming.T he insulin-like growth factors (IGF-I and -II) are essential for growth and development (1). Six high-affinity IGF-binding proteins (IGFBP-1 to IGFBP-6; refs. 2 and 3) strictly orchestrate IGF action. Despite their considerable sequence homology, each exhibits a discrete expression pattern and possesses an individual subset of motifs, signifying that although IGFBPs have common actions, they may also have unique properties.IGFBP-5 is the most conserved of the IGFBPs (4) and has been highlighted as a focal regulatory factor during the development of several key cell lineages, e.g., myoblasts (5) and neural cells (6, 7). In mice, Igfbp5 is expressed in the embryo from early development, principally in the myotomal component of the somites and developing central nervous system (8). Postnatally, serum IGFBP-5, in common with IGFBP-3, forms a ternary complex with IGF-I or IGF-II and the acid-labile subunit (9). Igfbp5 is up-regulated in the aggressive pediatric cancer, rhabdomyosarcoma (10), in the progression of prostate cancers to androgen independence (11), and in smooth muscle-derived uterine leiomyoma (12), indicating a function in neoplasia.IGFBP-5 initially binds IGFs with high affinity, principally by an N-terminal motif (13), and inhibits IGF activity by preventing IGF interaction with the type 1 receptor. It is further subject to regulated posttranslational modifications (3) to induce conformational changes that dec...

show abstract

Distinct expression patterns of insulin-like growth factor binding proteins 2 and 5 during fetal and postnatal development.

Cited by 91 publications

References 1 publication

cDNA microarrays detect activation of a myogenic transcription program by the PAX3-FKHR fusion oncogene

cDNA microarrays detect activation of a myogenic transcription program by the PAX3-FKHR fusion oncogene

Studies on insulin‐like growth factor‐I and insulin in chick limb morphogenesis

Insulin-like growth factor-binding protein 5 ( Igfbp5 ) compromises survival, growth, muscle development, and fertility in mice

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