Effects of insulin like growth factors on early embryonic chick limb myogenesis

Abstract

Limb muscles derive from pax3 expressing precursor cells that migrate from the hypaxial somite into the developing limb bud. Once there they begin to differentiate and express muscle determination genes such as MyoD. This process is regulated by a combination of inductive or inhibitory signals including Fgf18, retinoic acid, HGF, Notch and IGFs. IGFs are well known to affect late stages of muscle development and to promote both proliferation and differentiation. We examined their roles in early stage limb bud myogenesis using chicken embryos as an experimental model. Grafting beads soaked in purified recombinant IGF-I, IGF-II or small molecule inhibitors of specific signaling pathways into developing chick embryo limbs showed that both IGF-I and IGF-II induce expression of the early stage myogenic markers pax3 and MyoD as well as myogenin. Their effects on pax3 and MyoD expression were blocked by inhibitors of both the IGF type I receptor (picropodophyllotoxin, PPP) and MEK (U0126). The PI3K inhibitor LY294002 blocked IGF-II, but not IGF-I, induction of pax3 mRNA as well as the IGF-I, but not IGF-II, induction of MyoD mRNA. In addition SU5402, an FGFR/ VEGFR inhibitor, blocked the induction of MyoD by both IGFs but had no effect on pax3 induction, suggesting a role for FGF or VEGF signaling in their induction of MyoD. This was confirmed by in situ hybridization showing that FGF18, a known regulator of MyoD in limb myoblasts, was induced by IGF-I. In addition to their well-known effects on later stages of myogenesis via their induction of myogenin expression, both IGF-I and IGF-II induced pax3 and MyoD expression in developing chick embryos, indicating that they also regulate early stages of myogenesis. The data suggests that the IGFs may have slightly different effects on IGF1R signal transduction via PI3K and that their stimulatory effects on MyoD expression may be indirect, possibly via induction of FGF18 expression.

Engineering Biomimetic Materials for Skeletal Muscle Repair and Regeneration

“…During embryonic development and generation of skeletal muscle, numerous growth factors such as HGF and IGF are released in regular temporal and spatial patterns and modulate different myogenic signaling pathways such as Wnt, Notch, and sonic Hedgehog (Shh) . In adult skeletal muscle tissues, various growth factors regulate tissue hemostasis and regeneration by modulating the activation and differentiation of quiescent satellite cells and myoblasts .…”

Embryonic Chicken (Gallus gallus domesticus) as a Model of Cardiac Biology and Development

“…Embryonic chickens are a widely available model organism and have been used in a variety of research endeavors. Areas in which embryonic chickens have been used range from tissue patterning and symmetry, 4,6,98,138,146 cell migration, 1,8,16,75,76,96,121,168,174 vasculogenesis, 24,86 and specific organ system biology, such as cardiac morphogenesis 44,70,88,90,165 (which is the focus of this review). In addition to its wide use in developmental biology studies, embryonic chickens have also been used for studying cancer biology and cancer metastasis, 81,172 including cancer biology studies for malignancies affecting veterinary domestic species.…”

Effects of SW033291 on the myogenesis of muscle-derived stem cells and muscle regeneration

“…Recently, considerable efforts have been made towards the augmentation of seed cell expansion and differentiation, including mechanical stimulation, electrical stimulation, and biochemical activation by growth factors and other biomolecules, and the underlying molecular mechanism governing this process has also been elucidated to some degree [7]. Among biochemical stimulation approaches, growth factors such as hepatocyte growth factor (HGF) and insulin-like growth factor (IGF) have been demonstrated to regulate muscle tissue homeostasis and regeneration by modulating the proliferation and differentiation of satellite cells and myoblasts [8,9]. Other growth factors targeting the non-muscle components, including vascular endothelial growth factor (VEGF) and nerve growth factor (NGF), are also essential for developing a functional tissue [10][11][12].…”