The zebrafish HGF receptor met controls migration of myogenic progenitor cells in appendicular development

Abstract

The hepatocyte growth factor receptor C-met plays an important role in cellular migration, which is crucial for many developmental processes as well as for cancer cell metastasis. C-met has been linked to the development of mammalian appendicular muscle, which are derived from migrating muscle progenitor cells (MMPs) from within the somite. Mammalian limbs are homologous to the teleost pectoral and pelvic fins. In this study we used Crispr/Cas9 to mutate the zebrafish met gene and found that the MMP derived musculature of the paired appendages was severely affected. The mutation resulted in a reduced muscle fibre number, in particular in the pectoral abductor, and in a disturbed pectoral fin function. Other MMP derived muscles, such as the sternohyoid muscle and posterior hypaxial muscle were also affected in met mutants. This indicates that the role of met in MMP function and appendicular myogenesis is conserved within vertebrates.

Met is required for oligodendrocyte progenitor cell migration inDanio rerio

“…While a number of chemotactic molecules have been investigated in developmental OPC tiling, adult tiling and how it is maintained remains largely unknown. Another benefit of using zebrafish is that homozygous met mutants can live into adulthood and therefore, can be utilized to study these tiling processes in mature animals ( Nord et al 2019 ). It is possible that, while adult OPCs remain in their distinct domain with little migration, Met could be utilized in response to injury.…”

“…Because zebrafish embryos receive maternal mRNAs, including met mRNA from their mother ( Latimer and Jessen 2008 ), zebrafish met mutants successfully complete embryogenesis and can therefore be used to investigate later developmental processes, including OPC migration. In fact, many recent studies have used zebrafish embryos and larvae lacking Met function to study a number of development processes including motor axon targeting and migratory muscle precursor migration ( Nord et al 2019 ; Talbot et al 2019 ; Isabella et al 2020 ).…”

Met is required for oligodendrocyte progenitor cell migration in Danio rerio

“…The copyright holder for this preprint (which this version posted May 23, 2021. ; https://doi.org/10.1101/2021.05.21.445204 doi: bioRxiv preprint that homozygous met mutants can live into adulthood and therefore, can be utilized to study these tiling processes in mature animals (Nord et al 2019). It is possible that, while adult OPCs remain in their distinct domain with little migration, Met could be utilized in response to injury.…”

Retinoic acid organizes the vagus motor topographic map via spatiotemporal regulation of Hgf/Met signaling

“…Since this discovery, the detailed developmental mechanisms of several other major axon guidance signals has been elucidated (Bellon and Mann, 2018;Robichaux and Cowan, 2014;Stoeckli, 2017), while our understanding of how Hgf/Met regulates axon targeting decisions in the embryo has advanced comparatively little. This may be in part because in the limb, where the role of Hgf/Met signaling has been best studied, it has multiple successive functions: in the migration of muscle precursors into the limb (Bladt et al, 1995;Brand-Saberi et al, 1996;Haines et al, 2004;Nord et al, 2019;Talbot et al, 2019), in the formation of specific limb-innervating motor neuron pools (Helmbacher et al, 2003), in motor axon attraction (Ebens et al, 1996), and in motor neuron survival (Lamballe et al, 2011;Novak et al, 2000;Yamamoto et al, 1997). Hgf/Met is not required for the specification or survival of mX neurons, and although recent work has shown that Hgf/Met signaling is required for the migration of posterior PA-derived muscle progenitors to form esophageal muscle in the mouse (Comai et al, 2019), we do not observe any abnormalities in the formation of posterior PA muscle progenitors in the zebrafish hgfa or met mutants at the stages we studied here.…”