Fgf8 drives myogenic progression of a novel lateral fast muscle fibre population in zebrafish

Abstract

Fibroblast growth factors (Fgfs) have long been implicated in regulating vertebrate skeletal muscle differentiation, but their precise role(s) in vivo remain unclear. Here, we show that Fgf8 signalling in the somite is required for myod expression and terminal differentiation of a subset of fast muscle cells in the zebrafish lateral somite. In the absence of Fgf8, lateral somite cells transiently express myf5 but fail to make muscle and remain in a dermomyotome-like state characterised by pax3 and meox expression. Slow muscle fibres form and commence normal migration in the absence of Fgf8, but fail to traverse the expanded undifferentiated lateral somite. The Fgf8-independent residual population of medial fast muscle fibres is not Hedgehog dependent. However, Fgf8-independent medial fast muscle precursors are lacking in floatinghead mutants,suggesting that they require another ventral midline-derived signal. We conclude that Fgf8 drives terminal differentiation of a specific population of lateral muscle precursor cells within the early somite.

Alkali‐like myosin light chain‐1 (myl1) is an early marker for differentiating fast muscle cells in zebrafish

“…The expression of myl1 was decreased in ace mutants (Fig. 5), which correlates to the decreased expression of myod in the lateral part of the ace myotome, as previously described (Groves et al, 2005). The myl1 expression domain expanded into the adaxial cells in ubo mutants, which indicates that myl1 is transcriptionally repressed by Prdm1 in adaxial cells in wild type embryos (Fig.…”

“…Already at early gastrula stages, the lineage traces have concluded that mesodermal cells are predestined to either the slow or the fast pathway depending on their respective localization in the embryo (reviewed in Ochi and Westerfield, 2007). The myogenic fate, however, is determined during early somitogenesis by the inductive signals of FGF and hedgehog signalling pathways, where FGF signalling, at least in the lateral part of the presomitic mesoderm, results in fast muscle development and hedgehog signalling from the notochord leads to the specification of adaxial cells and slow fate Coutelle et al, 2001;Blagden et al, 1997;Lewis et al, 1999, Groves et al, 2005.…”

“…5). In FGF8a mutants (acerebellar, ace), the lateral part of the fast domain is lost at 24 hpf (Groves et al, 2005), and, consequently, this also leads to a reduction in myl1 expression, in particular in the lateral domain at the 15-somite stage (Fig. 5B).…”

“…The muscle precursors lateral to the adaxial cells will become the fasttwich fibres. Both slow and fast muscle precursors require the expression of the muscle regulatory factors, such as MyoD, Myf5, and myogenin (Coutelle et al, 2001;Groves et al, 2005;Hammond et al, 2007;Hinits et al, 2009), and the decision to become fast or slow is determined by the transcriptional repressor Prdm1, which is induced by hedgehog and acts by directly repressing genes that encode fast fibre-specific sarcomeric proteins in the adaxial cells (Roy et al, 2001, Baxendale et al, 2004von Hofsten et al, 2008). Prdm1 is also repressing the expression of sox6 in the adaxial cells and Sox6 is in turn repressing the slow specific genes in the fast domain (von Hofsten et al, 2008).…”

Myotome adaptability confers developmental robustness to somitic myogenesis in response to fibre number alteration

“…In parallel with this process, cells in the anterior somite border generate a Pax3/7-expressing DM external cell layer Groves et al, 2005;Hammond et al, 2007;Hollway et al, 2007;. Cells of the DM appear to contribute to later muscle growth .…”