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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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Inhibition of slow muscle  cells by a constitutively active isoform of PKA. (A) Whole-mount  Nomarski images showing slow  muscle cells labeled with the F59  antibody in a representative control  embryo. (B) Whole-mount Nomarski images showing slow muscle  cells labeled with the F59 antibody  in a representative embryo injected  with a constitutively active form of  PKA. (C) Section (dorsal to the  top) showing localization of slow  muscle cells labeled with F59 in a  control embryo. (D) Sections (dorsal to the top) showing local loss of  slow muscle cells in an embryo injected with a constitutively active  form of PKA.
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Figure 3: Inhibition of slow muscle cells by a constitutively active isoform of PKA. (A) Whole-mount Nomarski images showing slow muscle cells labeled with the F59 antibody in a representative control embryo. (B) Whole-mount Nomarski images showing slow muscle cells labeled with the F59 antibody in a representative embryo injected with a constitutively active form of PKA. (C) Section (dorsal to the top) showing localization of slow muscle cells labeled with F59 in a control embryo. (D) Sections (dorsal to the top) showing local loss of slow muscle cells in an embryo injected with a constitutively active form of PKA.

Mentions: Protein kinase A (PKA) is an integral part of the Hedgehog signaling pathway (for review see Perrimon, 1995). PKA constitutively represses Hedgehog target genes, and Hedgehog acts to relieve this repression. Thus, expression of a dominant negative isoform of PKA mimics Hedgehog signaling in both Drosophila (Jiang and Struhl, 1995; Li et al., 1995; Pan and Rubin, 1995) and in vertebrates (Fan et al., 1995; Hammerschmidt et al., 1996a; Ungar and Moon, 1996). Our results (Fig. 2) suggested that Hedgehog is sufficient to trigger slow muscle development. To test whether Hedgehog signaling is required for slow muscle development, we ectopically expressed the constitutively active PKA isoform (Orellana and McKnight, 1992). Compared with control embryos (Fig. 3 A), slow muscle cells labeled with F59 antibody appeared to be absent in embryos injected with RNA encoding the constitutively active isoform of PKA (Fig. 3 B). Frequently, injected RNAs are localized to one region of the embryo (Hammerschmidt et al., 1996a). Consistent with this, transverse sections through control (Fig. 3 C) and active PKA-injected embryos demonstrated a local loss of slow muscle cells in the active PKA injected embryos (Fig. 3 D). Together with the Hedgehog ectopic expression data (Fig. 2), this result suggests that Hedgehog signaling is required for the development of all slow muscle cells, including muscle pioneer cells (Hammerschmidt et al., 1996a, and data not shown).


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)

Inhibition of slow muscle  cells by a constitutively active isoform of PKA. (A) Whole-mount  Nomarski images showing slow  muscle cells labeled with the F59  antibody in a representative control  embryo. (B) Whole-mount Nomarski images showing slow muscle  cells labeled with the F59 antibody  in a representative embryo injected  with a constitutively active form of  PKA. (C) Section (dorsal to the  top) showing localization of slow  muscle cells labeled with F59 in a  control embryo. (D) Sections (dorsal to the top) showing local loss of  slow muscle cells in an embryo injected with a constitutively active  form of PKA.
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2139815&req=5

Figure 3: Inhibition of slow muscle cells by a constitutively active isoform of PKA. (A) Whole-mount Nomarski images showing slow muscle cells labeled with the F59 antibody in a representative control embryo. (B) Whole-mount Nomarski images showing slow muscle cells labeled with the F59 antibody in a representative embryo injected with a constitutively active form of PKA. (C) Section (dorsal to the top) showing localization of slow muscle cells labeled with F59 in a control embryo. (D) Sections (dorsal to the top) showing local loss of slow muscle cells in an embryo injected with a constitutively active form of PKA.
Mentions: Protein kinase A (PKA) is an integral part of the Hedgehog signaling pathway (for review see Perrimon, 1995). PKA constitutively represses Hedgehog target genes, and Hedgehog acts to relieve this repression. Thus, expression of a dominant negative isoform of PKA mimics Hedgehog signaling in both Drosophila (Jiang and Struhl, 1995; Li et al., 1995; Pan and Rubin, 1995) and in vertebrates (Fan et al., 1995; Hammerschmidt et al., 1996a; Ungar and Moon, 1996). Our results (Fig. 2) suggested that Hedgehog is sufficient to trigger slow muscle development. To test whether Hedgehog signaling is required for slow muscle development, we ectopically expressed the constitutively active PKA isoform (Orellana and McKnight, 1992). Compared with control embryos (Fig. 3 A), slow muscle cells labeled with F59 antibody appeared to be absent in embryos injected with RNA encoding the constitutively active isoform of PKA (Fig. 3 B). Frequently, injected RNAs are localized to one region of the embryo (Hammerschmidt et al., 1996a). Consistent with this, transverse sections through control (Fig. 3 C) and active PKA-injected embryos demonstrated a local loss of slow muscle cells in the active PKA injected embryos (Fig. 3 D). Together with the Hedgehog ectopic expression data (Fig. 2), this result suggests that Hedgehog signaling is required for the development of all slow muscle cells, including muscle pioneer cells (Hammerschmidt et al., 1996a, and data not shown).

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