Abstract
BackgroundNegative regulators of signal transduction cascades play critical roles in controlling different aspects of normal embryonic development. Sprouty2 (Spry2) negatively regulates receptor tyrosine kinases (RTK) and FGF signalling and is important in differentiation, cell migration and proliferation. In vertebrate embryos, Spry2 is expressed in paraxial mesoderm and in forming somites. Expression is maintained in the myotome until late stages of somite differentiation. However, its role and mode of action during somite myogenesis is still unclear.ResultsHere, we analysed chick Spry2 expression and showed that it overlaps with that of myogenic regulatory factors MyoD and Mgn. Targeted mis-expression of Spry2 led to inhibition of myogenesis, whilst its C-terminal domain led to an increased number of myogenic cells by stimulating cell proliferation.ConclusionsSpry2 is expressed in somite myotomes and its expression overlaps with myogenic regulatory factors. Overexpression and dominant-negative interference showed that Spry2 plays a crucial role in regulating chick myogenesis by fine tuning of FGF signaling through a negative feedback loop. We also propose that mir-23, mir-27 and mir-128 could be part of the negative feedback loop mechanism. Our analysis is the first to shed some light on in vivo Spry2 function during chick somite myogenesis.
Highlights
Negative regulators of signal transduction cascades play critical roles in controlling different aspects of normal embryonic development
Sprouty2 expression during somite myogenesis Spry2 expression during somite development was analysed at different Hamburger and Hamilton (HH) stages
At stage HH11 expression was restricted to the pre-segmented paraxial mesoderm (PSM) and in somites expression was very weak
Summary
Negative regulators of signal transduction cascades play critical roles in controlling different aspects of normal embryonic development. Sprouty (Spry2) negatively regulates receptor tyrosine kinases (RTK) and FGF signalling and is important in differentiation, cell migration and proliferation. Spry is expressed in paraxial mesoderm and in forming somites. Expression is maintained in the myotome until late stages of somite differentiation. In early vertebrate embryos, including the chick, somites form as paired structures from unsegmented paraxial mesoderm on either side of the neural tube. Cells in the ventral somite undergo an epithelial to mesenchymal transition (EMT) to form the sclerotome [1]. The dorsal part remains epithelial forming the dermomyotome, which generates the epaxial and hypaxial domains of the myotome. A network of signalling pathways and transcription factors coordinates the process of somite patterning and differentiation and how the myogenic programme in particular is activated differs in different parts of the body [3].
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