mRNA expression patterns of the IGF system during mouse limb bud development, determined by whole mount in situ hybridization

Kleffens, Marjolein van; Groffen, Cora; Rosato, Roberto R.; Eijnde, Stefan M. van den; Neck, Johan W. van; Lindenbergh-Kortleve, Dicky J.; Zwarthoff, Ellen C.; Drop, Stenvert L. S.

doi:10.1016/s0303-7207(98)00007-0

Cited by 40 publications

(34 citation statements)

References 57 publications

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“…In contrast, there was strong overlap of mRNA and peptide for IGFBP-2 and -4, which may indicate an autocrine or paracrine function for these binding proteins (IGFBP-1 mRNA and protein were confined to the liver). In addition, there is significant overlap of IGF axis mRNA expression patterns and regions of apoptotic activity, as measured by Nile blue staining, in both the head-neck region and limb bud (see below) of mouse embryos (van Kleffens et al, 1998). This finding is consistent with the function of IGFs as potent cell survival signals and of IGFBPs as regulators of this function.…”

Section: Mammalian Developmentsupporting

confidence: 65%

“…3). In fact, IGFBP-2 and -5 are the only two of the six binding proteins expressed in the AER (van Kleffens et al, 1998), and their expression at this site is consistent with them having a role in the directional outgrowth of limb mesenchyme. In addition to IGFBP-2 and -5, several members of the fibroblast growth factor (FGF) family, including FGF-2, -4 and -8 are expressed by the AER (Tickle, 1996).…”

Section: Expression Of the Igf Axis In The Mammalian Embryonic Limb Budmentioning

confidence: 64%

“…The mouse and rat limb buds provide the most obvious example of the overlap of IGFBP-2 and -5 mRNA expression, with both binding proteins displaying strong expression along the whole length of the AER and weaker expression in a proximal region of the bud (Pintar et al, 1991;Streck et al, 1992;Wood et al, 1992;Allan et al, 1998;van Kleffens et al, 1998;Fig. 3).…”

Section: Expression Of the Igf Axis In The Mammalian Embryonic Limb Budmentioning

confidence: 99%

“…There is increasing evidence that IGFBPs not only regulate IGF bioavailability, but that they also have their own receptors that mediate IGF-independent actions. Cell surface receptors for IGFBP-1 (Jones et al, 1993), IGFBP-2 (Rauschnabel et al, 1999), IGFBP-3 (Oh et al, 1993a) and IGFBP-5 (Andress, 1995, 1998 have been described, although, to date, none of these proteins have been cloned. Direct IGF-independent effects of IGFBPs include modulation of bone cell proliferation (Mohan et al, 1995) and growth arrest of breast and prostate cancer cells (Oh et The insulin-like growth factor (IGF) axis has been studied extensively in the developing vertebrate embryo.…”

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confidence: 99%

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Insulin-like growth factor axis during embryonic development

Allan¹,

Flint²,

Patel³

2001

Reproduction

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The insulin-like growth factor (IGF) axis has been studied extensively in the developing vertebrate embryo. Knockout experiments have demonstrated that both IGF-I and -II are required for normal development in the mouse embryo, and mRNA and protein expression patterns for both growth factors, together with those for the type I IGF receptor and the six IGF-binding proteins, have been analysed in embryos from different species. Although the unique temporal and spatial expression patterns of these genes indicates important roles for the IGF axis during organ and whole animal development, the variation and complexity of expression makes these roles difficult to unravel. However, one possible mechanism unifying the IGF system in development is programmed cell death (apoptosis), which has been shown to be important in sculpting embryonic tissues, and, in particular, the developing limb bud. In addition, the very early onset of expression of various IGF family members in chicken embryos further emphasizes the fundamental importance of this system in development. This article reviews the work that has been carried out in this area in the context of current understanding of the IGF system.

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Section: Mammalian Developmentsupporting

confidence: 65%

Section: Expression Of the Igf Axis In The Mammalian Embryonic Limb Budmentioning

confidence: 64%

Section: Expression Of the Igf Axis In The Mammalian Embryonic Limb Budmentioning

confidence: 99%

mentioning

confidence: 99%

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Insulin-like growth factor axis during embryonic development

Allan¹,

Flint²,

Patel³

2001

Reproduction

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“…In other cases the function of secreted factors in the regressing interdigits is less understood. Diferent Slit ligands and their Robo receptors are expressed in the interdigits without a known functional significance (Vargesson et al, 2001).The participation of IGF-signaling in the control of interdigital cell death was also proposed on the basis of the interdigital expression of different members of the pathway during the stages of interdigital cell death (van Kleffens et al, 1998;Allan et al, 2001). However, gain-and loss-of-function mutations of this signalling pathway cause phenotypes related with growth rather than altered morphogenesis (see, Tripathi et al, 2009).…”

Section: Regulation Of Interdigital Tissue Regressionmentioning

confidence: 99%

Interdigital tissue regression in the developing limb of vertebrates

Lorda‐Diez¹,

Montero²,

García‐Porrero³

et al. 2015

Int. J. Dev. Biol.

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Here we have chosen the regression of the interdigital tissue which sculpts the digits from the hand/foot plate in tetrapod embryos to review the most relevant aspects concerning the regulation and biological significance of programmed cell death. We gather abundant information showing that the initiation of the degenerative process is the result of a complex interplay between the different signaling pathways which are also responsible for limb outgrowth and skeletal tissue differentiation, rather than being regulated by a specific signaling pathway. The model further shows that once the death response is triggered, several different routes of cell disruption, including caspase-dependent apoptosis, lysosomal-mediated cell death, and even a cell senescence process, are activated in the interdigits to ensure their elimination. Transcriptional and structural changes accompanying the degenerative process, and their posible contribution to the control of the death process, are also revised in detail. Finally we survey a number of issues still awaiting clarification, such as the functional implication of interdigital cell death as a source of signals acting on the surrounding tissues, as occurs in the so called "regenerative cell death".

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Insulin‐like growth factor I stimulates myoblast expansion and myofiber development in the limb

Mitchell

Johnson

Hannon

2001

Developmental Dynamics

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Insulin-like growth factor I (IGF-I) is expressed in the anterior and posterior mesodermal cells of the developing limb. However, a definite role for IGF-I during early limb organogenesis is unknown. To determine the inherent participation of IGF-I during limb organ development, a retroviral delivery system (RCAS) was used to overexpress IGF-I throughout the developing hind limb of stage 24 chicken embryos. The area of the belly of the external gastrocnemius muscle in the IGF-I infected limb was an average of 160, 90, 70, and 80% larger than the contralateral control muscle belly, 4, 5, 6, and 7 days postinjection, respectively (all differences P < 0.01). In comparison to the contralateral control muscles, there were a significantly greater number of muscle fibers in the IGF-I infected muscles (P < 0.05), confirming that the majority of IGF-I-mediated muscle enlargement was due to an increase in total fiber numbers (hyperplasia). Four days postinjection, there was a 32% increase in myoblast to myofiber ratio in the muscle of injected limbs compared with the muscle in the contralateral noninjected control limbs (P < 0.05). This result demonstrates that IGF-I acts to expand the undifferentiated myoblast population, and as a result, more myofibers subsequently develop, and the muscles expressing ectopic IGF-I are enlarged by means of hyperplasia. There was no difference in tibiotarsus and fibula length or diameter between the IGF-I injected and control limb, suggesting that ectopic IGF-I expression within the mesoderm was not a nonspecific growth stimulant of all tissues of the developing limb, but specifically enhanced skeletal muscle development and growth. Ectopic IGF-I expression had no significant effect on myostatin mRNA concentrations. Our results support a model where mesodermally expressed IGF-I acts to regulate the number of primary myofibers, and, therefore, size of skeletal muscles, which form during the initial events of limb myogenesis.

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mRNA expression patterns of the IGF system during mouse limb bud development, determined by whole mount in situ hybridization

Cited by 40 publications

References 57 publications

Insulin-like growth factor axis during embryonic development

Insulin-like growth factor axis during embryonic development

Interdigital tissue regression in the developing limb of vertebrates

Insulin‐like growth factor I stimulates myoblast expansion and myofiber development in the limb

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