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Hedgehog Signaling during Appendage Development and Regeneration.

Singh BN, Koyano-Nakagawa N, Donaldson A, Weaver CV, Garry MG, Garry DJ - Genes (Basel) (2015)

Bottom Line: Relative to mammals, lower vertebrates, including zebrafish and newts, have a tremendous regenerative capacity to repair and regenerate a number of organs including: appendages, retina, heart, jaw and nervous system.Elucidation of the pathways that govern regeneration in these lower organisms may provide cues that will enhance the capacity for the regeneration of mammalian organs.Signaling pathways, such as the hedgehog pathway, have been shown to play critical functions during development and during regeneration in lower organisms.

View Article: PubMed Central - PubMed

Affiliation: Lillehei Heart Institute, University of Minnesota, Minneapolis, MN 55455, USA. bnsingh@umn.edu.

ABSTRACT
Regulatory networks that govern embryonic development have been well defined. While a common hypothesis supports the notion that the embryonic regulatory cascades are reexpressed following injury and tissue regeneration, the mechanistic regulatory pathways that mediate the regenerative response in higher organisms remain undefined. Relative to mammals, lower vertebrates, including zebrafish and newts, have a tremendous regenerative capacity to repair and regenerate a number of organs including: appendages, retina, heart, jaw and nervous system. Elucidation of the pathways that govern regeneration in these lower organisms may provide cues that will enhance the capacity for the regeneration of mammalian organs. Signaling pathways, such as the hedgehog pathway, have been shown to play critical functions during development and during regeneration in lower organisms. These signaling pathways have been shown to modulate multiple processes including cellular origin, positional identity and cellular maturation. The present review will focus on the cellular and molecular regulation of the hedgehog (HH) signaling pathway and its interaction with other signaling factors during appendage development and regeneration.

No MeSH data available.


Related in: MedlinePlus

Sequence of regenerative events and HH signaling. Longitudinal section of an unamputated and regenerating fin ray showing the basal layer (blue) and outer epidermis (yellow). Epidermal cells cover the wound and mesenchymal cells from the stump proliferate and migrate distally to form the blastema. HH signaling is induced in the lateral basal epidermal layer and a signaling center (green) in the apical region (yellow) that includes: FGF, WNT and BMP signaling leads to the induction of cellular proliferation (blue) and regeneration. Note the key is in the upper panel.
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genes-06-00417-f004: Sequence of regenerative events and HH signaling. Longitudinal section of an unamputated and regenerating fin ray showing the basal layer (blue) and outer epidermis (yellow). Epidermal cells cover the wound and mesenchymal cells from the stump proliferate and migrate distally to form the blastema. HH signaling is induced in the lateral basal epidermal layer and a signaling center (green) in the apical region (yellow) that includes: FGF, WNT and BMP signaling leads to the induction of cellular proliferation (blue) and regeneration. Note the key is in the upper panel.

Mentions: Teleost fish have a tremendous capacity to regenerate a variety of tissues including heart, spinal cord and fin [27,28,85,86]. Upon amputation, fin regeneration occurs in three distinct stages including: wound healing, blastema formation and regeneration (regrowth) from the plane of amputation. Transcriptional profiling during fin regeneration revealed differential gene expression associated with these distinct stages in zebrafish [27,86]. These differential molecular programs included a number of developmental transcripts and signaling factors involved in regulating fin growth such as Fgf, Bmp2b, β-catenin, Shh, Hoxa11b and Hoxa13b [17,25,48,86]. In the wound epidermis, early expression of WNT signaling factors regulate the formation of the thickened epidermis termed the epidermal cap [17,25]. The proliferative response of the epidermal cells results in the formation of the thickened epidermal cap. Recently, Lee et al. described the existence of distinct types of cells beneath the epidermal layer which defines the regional expression domain for Shh signaling (Figure 4) [86]. FGF signaling in the adjacent layer helps localize and maintain Shh expression in the proximal region of the regenerating fin, whereas in the distal region, the expression of Shh is reduced by a Ras-Wnt5b signaling mechanism [25,86]. These findings suggest a critical role for epidermal signals in the control of the signaling domain during the regenerative response (Figure 4).


Hedgehog Signaling during Appendage Development and Regeneration.

Singh BN, Koyano-Nakagawa N, Donaldson A, Weaver CV, Garry MG, Garry DJ - Genes (Basel) (2015)

Sequence of regenerative events and HH signaling. Longitudinal section of an unamputated and regenerating fin ray showing the basal layer (blue) and outer epidermis (yellow). Epidermal cells cover the wound and mesenchymal cells from the stump proliferate and migrate distally to form the blastema. HH signaling is induced in the lateral basal epidermal layer and a signaling center (green) in the apical region (yellow) that includes: FGF, WNT and BMP signaling leads to the induction of cellular proliferation (blue) and regeneration. Note the key is in the upper panel.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4488672&req=5

genes-06-00417-f004: Sequence of regenerative events and HH signaling. Longitudinal section of an unamputated and regenerating fin ray showing the basal layer (blue) and outer epidermis (yellow). Epidermal cells cover the wound and mesenchymal cells from the stump proliferate and migrate distally to form the blastema. HH signaling is induced in the lateral basal epidermal layer and a signaling center (green) in the apical region (yellow) that includes: FGF, WNT and BMP signaling leads to the induction of cellular proliferation (blue) and regeneration. Note the key is in the upper panel.
Mentions: Teleost fish have a tremendous capacity to regenerate a variety of tissues including heart, spinal cord and fin [27,28,85,86]. Upon amputation, fin regeneration occurs in three distinct stages including: wound healing, blastema formation and regeneration (regrowth) from the plane of amputation. Transcriptional profiling during fin regeneration revealed differential gene expression associated with these distinct stages in zebrafish [27,86]. These differential molecular programs included a number of developmental transcripts and signaling factors involved in regulating fin growth such as Fgf, Bmp2b, β-catenin, Shh, Hoxa11b and Hoxa13b [17,25,48,86]. In the wound epidermis, early expression of WNT signaling factors regulate the formation of the thickened epidermis termed the epidermal cap [17,25]. The proliferative response of the epidermal cells results in the formation of the thickened epidermal cap. Recently, Lee et al. described the existence of distinct types of cells beneath the epidermal layer which defines the regional expression domain for Shh signaling (Figure 4) [86]. FGF signaling in the adjacent layer helps localize and maintain Shh expression in the proximal region of the regenerating fin, whereas in the distal region, the expression of Shh is reduced by a Ras-Wnt5b signaling mechanism [25,86]. These findings suggest a critical role for epidermal signals in the control of the signaling domain during the regenerative response (Figure 4).

Bottom Line: Relative to mammals, lower vertebrates, including zebrafish and newts, have a tremendous regenerative capacity to repair and regenerate a number of organs including: appendages, retina, heart, jaw and nervous system.Elucidation of the pathways that govern regeneration in these lower organisms may provide cues that will enhance the capacity for the regeneration of mammalian organs.Signaling pathways, such as the hedgehog pathway, have been shown to play critical functions during development and during regeneration in lower organisms.

View Article: PubMed Central - PubMed

Affiliation: Lillehei Heart Institute, University of Minnesota, Minneapolis, MN 55455, USA. bnsingh@umn.edu.

ABSTRACT
Regulatory networks that govern embryonic development have been well defined. While a common hypothesis supports the notion that the embryonic regulatory cascades are reexpressed following injury and tissue regeneration, the mechanistic regulatory pathways that mediate the regenerative response in higher organisms remain undefined. Relative to mammals, lower vertebrates, including zebrafish and newts, have a tremendous regenerative capacity to repair and regenerate a number of organs including: appendages, retina, heart, jaw and nervous system. Elucidation of the pathways that govern regeneration in these lower organisms may provide cues that will enhance the capacity for the regeneration of mammalian organs. Signaling pathways, such as the hedgehog pathway, have been shown to play critical functions during development and during regeneration in lower organisms. These signaling pathways have been shown to modulate multiple processes including cellular origin, positional identity and cellular maturation. The present review will focus on the cellular and molecular regulation of the hedgehog (HH) signaling pathway and its interaction with other signaling factors during appendage development and regeneration.

No MeSH data available.


Related in: MedlinePlus