The transcription factor Six1a plays an essential role in the craniofacial myogenesis of zebrafish

Abstract

Transcription factor Six1a plays important roles in morphogenesis, organogenesis, and cell differentiation. However, the role of Six1a during zebrafish cranial muscle development is still unclear. Here, we demonstrated that Six1a was required for sternohyoideus, medial rectus, inferior rectus, and all pharyngeal arch muscle development. Although Six1a was also necessary for myod and myogenin expression in head muscles, it did not affect myf5 expression in cranial muscles that originate from head mesoderm. Overexpression of myod enabled embryos to rescue all the defects in cranial muscles induced by injection of six1a-morpholino (MO), suggesting that myod is directly downstream of six1a in controlling craniofacial myogenesis. However, overexpression of six1a was unable to rescue arch muscle defects in the tbx1- and myf5-morphants, suggesting that six1a is only involved in myogenic maintenance, not its initiation, during arch muscle myogenesis. Although the craniofacial muscle defects caused by pax3-MO phenocopied those induced by six1a-MO, injection of six1a, myod or myf5 mRNA did not rescue the cranial muscle defects in pax3 morphants, suggesting that six1a and pax3 do not function in the same regulatory network. Therefore, we proposed four putative regulatory pathways to understand how six1a distinctly interacts with either myf5 or myod during zebrafish craniofacial muscle development.

Six1 regulates proliferation of Pax7+ muscle progenitors in zebrafish

“…S2). In addition to having an imperative effect on cranial muscle formation as previously described for Six1b (Lin et al, 2009), knock down of both Six1a and Six1b reduced the fast muscle domain significantly ( Fig. 2A,B).…”

“…In zebrafish, there are two six1 genes, named six1a and six1b. Studies have been performed on six1b under the previous name six1a (Bessarab et al, 2008;Lin et al, 2009). In contrast to mammalian Six1, the zebrafish six1b morphant embryos alone show a severe muscle phenotype, in particular in the craniofacial region, where they completely lack fast muscle fibre (Lin et al, 2009).…”

“…Studies have been performed on six1b under the previous name six1a (Bessarab et al, 2008;Lin et al, 2009). In contrast to mammalian Six1, the zebrafish six1b morphant embryos alone show a severe muscle phenotype, in particular in the craniofacial region, where they completely lack fast muscle fibre (Lin et al, 2009). six1b morphants have a reduced expression of several fast muscle markers, such as isoforms of the fast muscle specific myosin heavy chains and a-tropomyosin (tpma) (Bessarab et al, 2008).…”

“…six1b morphants have a reduced expression of several fast muscle markers, such as isoforms of the fast muscle specific myosin heavy chains and a-tropomyosin (tpma) (Bessarab et al, 2008). In addition, Six1b has been shown to be essential for the formation of cranial and pectoral fin muscle (Lin et al, 2009). Six1 in mammals has also been shown to regulate the expression of Pax3 (Grifone et al, 2005), which is expressed together with Pax7 in the majority of the dermomyotomal cells (Relaix et al, 2005), but the specific role of Six1 in the Pax7 + cells in zebrafish has not been determined.…”

An eye on the head: the development and evolution of craniofacial muscles

“…Although Meox1 and Meox2 have roles in somite formation and differentiation, intriguingly, subsets of proximal and distal forelimb muscles are missing in Meox2 mutants, and overall fore-and hindlimb muscle masses are reduced (Mankoo et al, 1999;Mankoo et al, 2003). In fact, Six1 has been implicated in head muscle development in zebrafish (Lin et al, 2009). In spite of this complexity in the gene regulatory network upstream of the MRFs, one could speculate that two or more distinct regulatory cascades at the level of mesoderm specification might have evolved to regulate the MRFs and to orchestrate myogenesis.…”