The homeobox gene Msx in development and transdifferentiation of jellyfish striated muscle

Abstract

Bilaterian Msx homeobox genes are generally expressed in areas of cell proliferation and in association with multipotent progenitor cells. Likewise, jellyfish Msx is expressed in progenitor cells of the developing entocodon, a cell layer giving rise to the striated and smooth muscles of the medusa. However, in contrast to the bilaterian homologs, Msx gene expression is maintained at high levels in the differentiated striated muscle of the medusa in vivo and in vitro. This tissue exhibits reprogramming competence. Upon induction, the Msx gene is immediately switched off in the isolated striated muscle undergoing transdifferentiation, to be upregulated again in the emerging smooth muscle cells which, in a stem cell like manner, undergo quantal cell divisions producing two cell types, a proliferating smooth muscle cell and a differentiating nerve cell. This study indicates that the Msx protein may be a key component of the reprogramming machinery responsible for the extraordinary transdifferentation and regeneration potential of striated muscle in the hydrozoan jellyfish.

BMP2/4 and BMP5-8 in jellyfish development and transdifferentiation

“…Thus, the jellyfish BMPs may induce muscle specific genes in the adjacent developing muscle tissues (Fig. 5), in particular the Brachyury and Msx genes (Spring et al, 2002;Galle et al, 2005). A similar situation is found in mammals where BMP4 activates the mesoderm marker Brachyury (Winnier et al, 1995) and the Msx1 gene during neural crest induction (Tribulo et al, 2003).…”

“…This may be attributed to the evolutionary introduction of the polyp stage into the life cycle of a preexisting jellyfish ancestor with direct development thereby splitting medusa development at gastrulation, with the first part consisting of larva and polyp formation separated from the second part with entocodon (mesoderm-like layer) development in the differentiating medusa as previously Schematic representation of in situ staining patterns in a quarter cross section of medusa bud stage 6-7. More detailed expression patterns for mesodermal genes are published for Twist (Spring et al, 2000), Brachyury (Spring et al, 2002), Msx (Galle et al, 2005) and others (Seipel and Schmid, 2005 and references therein).…”

“…Growth factors, in turn, control cell proliferation and differentiation, as well as synthesis and remodeling of the ECM. In the jellyfish experimental system BMP5-8 gene activity is highest shortly after enzymatic treatment of the isolated muscle and transcription is maintained at significant levels in the first 17hrs of transdifferentiation, when expression of muscle specific genes like Msx (Galle et al, 2005) and Tpm2 (Seipel et al, 2004a) is shut down before cell morphology and cycle status are changed. The prolonged BMP5-8 expression may reflect a continuous BMP5-8 growth factor requirement for the early stages of the transdifferentiation process before upregulation of the stem cell gene Ciwi (Seipel et al, 2004b).…”

Vertebrate-like regeneration in the invertebrate chordate amphioxus

“…The analyses were performed using complete growth datasets from 64 animals (48 small and 16 large) collected at timepoints 14,21,28,35,42,49, and 56 d postamputation. The regeneration data were fitted to a Gompertz function (SI Materials and Methods).…”

“…To begin to understand the molecular basis of the regenerative process in chordates, we identified conserved and divergent characters in amphioxus. The msx homeobox transcription factors are downstream targets of bone morphogenetic protein (BMP) signaling, and orthologs are expressed during head regeneration in planaria, in tail and limb regeneration in a variety of vertebrates, and during muscle transdifferentiation in jellyfish (20)(21)(22)(23). In amphioxus, msx is expressed in the undifferentiated cells of the notochord, neural tube ampulla, and blastema mesenchyme by stage 2 as well as the wound epithelium (Fig.…”