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Positive and negative regulation of muscle cell identity by members of the hedgehog and TGF-beta gene families.

Du SJ, Devoto SH, Westerfield M, Moon RT - J. Cell Biol. (1997)

Bottom Line: We have examined whether the development of embryonic muscle fiber type is regulated by competing influences between Hedgehog and TGF-beta signals, as previously shown for development of neuronal cell identity in the neural tube.We found that ectopic expression of Hedgehogs or inhibition of protein kinase A in zebrafish embryos induces slow muscle precursors throughout the somite but muscle pioneer cells only in the middle of the somite.We propose that a Hedgehog signal first induces the formation of slow muscle precursor cells, and subsequent Hedgehog and TGF-beta signals exert competing positive and negative influences on the development of muscle pioneer cells.

View Article: PubMed Central - PubMed

Affiliation: Howard Hughes Medical Institute, University of Washington, School of Medicine, Seattle 98195, USA.

ABSTRACT
We have examined whether the development of embryonic muscle fiber type is regulated by competing influences between Hedgehog and TGF-beta signals, as previously shown for development of neuronal cell identity in the neural tube. We found that ectopic expression of Hedgehogs or inhibition of protein kinase A in zebrafish embryos induces slow muscle precursors throughout the somite but muscle pioneer cells only in the middle of the somite. Ectopic expression in the notochord of Dorsalin-1, a member of the TGF-beta superfamily, inhibits the formation of muscle pioneer cells, demonstrating that TGF-beta signals can antagonize the induction of muscle pioneer cells by Hedgehog. We propose that a Hedgehog signal first induces the formation of slow muscle precursor cells, and subsequent Hedgehog and TGF-beta signals exert competing positive and negative influences on the development of muscle pioneer cells.

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Opposing actions of  Hedgehog and BMP4-like proteins regulate slow muscle cell  identity. (A) At the tail bud  stage, paraxial mesoderm cells  are induced by Hedgehog secreted from notochord precursor cells to become adaxial cells,  the slow muscle precursors. A  subset of the adaxial cells located adjacent to the notochord  are induced to become muscle  pioneer cells by continued Hedgehog signal from the notochord  cells and floor plate cells. In contrast, other slow muscle precursors migrate to the lateral surface  of the myotome and differentiate into non–muscle pioneer  slow muscle cells. BMP4-like inhibitory signal antagonizes the  hedgehog signals in dorsal and ventral regions of the somite and blocks the induction of muscle pioneer cells in these regions. (B) Schematic illustration of this model in cross section at the tailbud stage (upper embryo, arrow denotes Hedgehog signal), and at the somitogenesis stage (lower embryo, arrow denotes Hedgehog signal and stippling denotes the BMP4-like signal). The distribution of muscle pioneers is determined by the distribution of these competing signals.
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Figure 8: Opposing actions of Hedgehog and BMP4-like proteins regulate slow muscle cell identity. (A) At the tail bud stage, paraxial mesoderm cells are induced by Hedgehog secreted from notochord precursor cells to become adaxial cells, the slow muscle precursors. A subset of the adaxial cells located adjacent to the notochord are induced to become muscle pioneer cells by continued Hedgehog signal from the notochord cells and floor plate cells. In contrast, other slow muscle precursors migrate to the lateral surface of the myotome and differentiate into non–muscle pioneer slow muscle cells. BMP4-like inhibitory signal antagonizes the hedgehog signals in dorsal and ventral regions of the somite and blocks the induction of muscle pioneer cells in these regions. (B) Schematic illustration of this model in cross section at the tailbud stage (upper embryo, arrow denotes Hedgehog signal), and at the somitogenesis stage (lower embryo, arrow denotes Hedgehog signal and stippling denotes the BMP4-like signal). The distribution of muscle pioneers is determined by the distribution of these competing signals.

Mentions: We propose that early signaling by Hedgehogs is sufficient to trigger the development of slow muscle identity, but that muscle pioneer development requires additional later exposure to Hedgehogs (Fig. 8 A). This hypothesis is supported by the following observations. First, slow muscle precursors are distinct from the other presomitic cells before muscle pioneers become distinct from the other slow muscle precursors. Second, injection of Hedgehog RNA was consistently more effective at inducing non– muscle pioneer slow muscle cells than muscle pioneer cells. Third, hedgehog RNA injection induces muscle pioneers more effectively in anterior somites than in posterior somites of the embryo (data not shown). If the injected hedgehog RNA is degraded over time, then there would consistently be more ectopic hedgehog early in development (in anterior somites) than there would be later in development (in posterior somites). Finally, in several mutants (no tail, floating head), Hedgehog expression becomes progressively reduced, relative to wild-type embryos, as development proceeds. In these mutants, muscle pioneers are missing, whereas other slow muscle cells develop relatively normally, especially in the earlier developing anterior somites (Devoto et al., 1996a).


Positive and negative regulation of muscle cell identity by members of the hedgehog and TGF-beta gene families.

Du SJ, Devoto SH, Westerfield M, Moon RT - J. Cell Biol. (1997)

Opposing actions of  Hedgehog and BMP4-like proteins regulate slow muscle cell  identity. (A) At the tail bud  stage, paraxial mesoderm cells  are induced by Hedgehog secreted from notochord precursor cells to become adaxial cells,  the slow muscle precursors. A  subset of the adaxial cells located adjacent to the notochord  are induced to become muscle  pioneer cells by continued Hedgehog signal from the notochord  cells and floor plate cells. In contrast, other slow muscle precursors migrate to the lateral surface  of the myotome and differentiate into non–muscle pioneer  slow muscle cells. BMP4-like inhibitory signal antagonizes the  hedgehog signals in dorsal and ventral regions of the somite and blocks the induction of muscle pioneer cells in these regions. (B) Schematic illustration of this model in cross section at the tailbud stage (upper embryo, arrow denotes Hedgehog signal), and at the somitogenesis stage (lower embryo, arrow denotes Hedgehog signal and stippling denotes the BMP4-like signal). The distribution of muscle pioneers is determined by the distribution of these competing signals.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2139815&req=5

Figure 8: Opposing actions of Hedgehog and BMP4-like proteins regulate slow muscle cell identity. (A) At the tail bud stage, paraxial mesoderm cells are induced by Hedgehog secreted from notochord precursor cells to become adaxial cells, the slow muscle precursors. A subset of the adaxial cells located adjacent to the notochord are induced to become muscle pioneer cells by continued Hedgehog signal from the notochord cells and floor plate cells. In contrast, other slow muscle precursors migrate to the lateral surface of the myotome and differentiate into non–muscle pioneer slow muscle cells. BMP4-like inhibitory signal antagonizes the hedgehog signals in dorsal and ventral regions of the somite and blocks the induction of muscle pioneer cells in these regions. (B) Schematic illustration of this model in cross section at the tailbud stage (upper embryo, arrow denotes Hedgehog signal), and at the somitogenesis stage (lower embryo, arrow denotes Hedgehog signal and stippling denotes the BMP4-like signal). The distribution of muscle pioneers is determined by the distribution of these competing signals.
Mentions: We propose that early signaling by Hedgehogs is sufficient to trigger the development of slow muscle identity, but that muscle pioneer development requires additional later exposure to Hedgehogs (Fig. 8 A). This hypothesis is supported by the following observations. First, slow muscle precursors are distinct from the other presomitic cells before muscle pioneers become distinct from the other slow muscle precursors. Second, injection of Hedgehog RNA was consistently more effective at inducing non– muscle pioneer slow muscle cells than muscle pioneer cells. Third, hedgehog RNA injection induces muscle pioneers more effectively in anterior somites than in posterior somites of the embryo (data not shown). If the injected hedgehog RNA is degraded over time, then there would consistently be more ectopic hedgehog early in development (in anterior somites) than there would be later in development (in posterior somites). Finally, in several mutants (no tail, floating head), Hedgehog expression becomes progressively reduced, relative to wild-type embryos, as development proceeds. In these mutants, muscle pioneers are missing, whereas other slow muscle cells develop relatively normally, especially in the earlier developing anterior somites (Devoto et al., 1996a).

Bottom Line: We have examined whether the development of embryonic muscle fiber type is regulated by competing influences between Hedgehog and TGF-beta signals, as previously shown for development of neuronal cell identity in the neural tube.We found that ectopic expression of Hedgehogs or inhibition of protein kinase A in zebrafish embryos induces slow muscle precursors throughout the somite but muscle pioneer cells only in the middle of the somite.We propose that a Hedgehog signal first induces the formation of slow muscle precursor cells, and subsequent Hedgehog and TGF-beta signals exert competing positive and negative influences on the development of muscle pioneer cells.

View Article: PubMed Central - PubMed

Affiliation: Howard Hughes Medical Institute, University of Washington, School of Medicine, Seattle 98195, USA.

ABSTRACT
We have examined whether the development of embryonic muscle fiber type is regulated by competing influences between Hedgehog and TGF-beta signals, as previously shown for development of neuronal cell identity in the neural tube. We found that ectopic expression of Hedgehogs or inhibition of protein kinase A in zebrafish embryos induces slow muscle precursors throughout the somite but muscle pioneer cells only in the middle of the somite. Ectopic expression in the notochord of Dorsalin-1, a member of the TGF-beta superfamily, inhibits the formation of muscle pioneer cells, demonstrating that TGF-beta signals can antagonize the induction of muscle pioneer cells by Hedgehog. We propose that a Hedgehog signal first induces the formation of slow muscle precursor cells, and subsequent Hedgehog and TGF-beta signals exert competing positive and negative influences on the development of muscle pioneer cells.

Show MeSH
Related in: MedlinePlus