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Distinct functional and temporal requirements for zebrafish Hdac1 during neural crest-derived craniofacial and peripheral neuron development.

Ignatius MS, Unal Eroglu A, Malireddy S, Gallagher G, Nambiar RM, Henion PD - PLoS ONE (2013)

Bottom Line: In the peripheral nervous system, there is a disruption of enteric, DRG and sympathetic neuron differentiation in hdac1(b382) mutants compared to wildtype embryos.Sympathetic neuron precursors are specified in hdac1(b382) mutants and they undergo generic neuronal differentiation but fail to undergo noradrenergic differentiation.Using the HDAC inhibitor TSA, we isolated enzyme activity and temporal requirements for HDAC function that reproduce hdac1(b382) defects in craniofacial and sympathetic neuron development.

View Article: PubMed Central - PubMed

Affiliation: Molecular, Cellular and Developmental Biology Program, Ohio State University, Columbus, Ohio, United States of America.

ABSTRACT
The regulation of gene expression is accomplished by both genetic and epigenetic means and is required for the precise control of the development of the neural crest. In hdac1(b382) mutants, craniofacial cartilage development is defective in two distinct ways. First, fewer hoxb3a, dlx2 and dlx3-expressing posterior branchial arch precursors are specified and many of those that are consequently undergo apoptosis. Second, in contrast, normal numbers of progenitors are present in the anterior mandibular and hyoid arches, but chondrocyte precursors fail to terminally differentiate. In the peripheral nervous system, there is a disruption of enteric, DRG and sympathetic neuron differentiation in hdac1(b382) mutants compared to wildtype embryos. Specifically, enteric and DRG-precursors differentiate into neurons in the anterior gut and trunk respectively, while enteric and DRG neurons are rarely present in the posterior gut and tail. Sympathetic neuron precursors are specified in hdac1(b382) mutants and they undergo generic neuronal differentiation but fail to undergo noradrenergic differentiation. Using the HDAC inhibitor TSA, we isolated enzyme activity and temporal requirements for HDAC function that reproduce hdac1(b382) defects in craniofacial and sympathetic neuron development. Our study reveals distinct functional and temporal requirements for zebrafish hdac1 during neural crest-derived craniofacial and peripheral neuron development.

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Treatment with the HDAC inhibitor TSA can reproduce the hdac1b382 mutant phenotype.A–d Lateral views of wild-type embryos treated with DMSO, 400 nM, 600 nM and 800 nM TSA from 16–24 hpf after which embryos were fixed and stained for dlx2 expression. A–D and A’–D’ Alcian blue stained 3.5 dpf wild-type embryos under different TSA treatment conditions, all embryos were treated between 16 hpf and 3.5 dpf after which embryos were fixed and then stained with alcian blue; A–A’ DMSO controls, B–B’ 400 nM TSA, C–C’ 600 nM TSA, D–D’ 800 nM TSA. A–D lateral view; A’–D’ ventral views. A’’–D’’ schematic with summary of craniofacial defects at different TSA treatment conditions. M, mandibular; H, hyoid; cb1-5, cerato-branchials 1-5; BA, branchial arches,+++ wild-type,++ reduced in size compared to wild-type,+severely reduced compared to wild-type, +/− severely reduced or absent altogether.
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pone-0063218-g004: Treatment with the HDAC inhibitor TSA can reproduce the hdac1b382 mutant phenotype.A–d Lateral views of wild-type embryos treated with DMSO, 400 nM, 600 nM and 800 nM TSA from 16–24 hpf after which embryos were fixed and stained for dlx2 expression. A–D and A’–D’ Alcian blue stained 3.5 dpf wild-type embryos under different TSA treatment conditions, all embryos were treated between 16 hpf and 3.5 dpf after which embryos were fixed and then stained with alcian blue; A–A’ DMSO controls, B–B’ 400 nM TSA, C–C’ 600 nM TSA, D–D’ 800 nM TSA. A–D lateral view; A’–D’ ventral views. A’’–D’’ schematic with summary of craniofacial defects at different TSA treatment conditions. M, mandibular; H, hyoid; cb1-5, cerato-branchials 1-5; BA, branchial arches,+++ wild-type,++ reduced in size compared to wild-type,+severely reduced compared to wild-type, +/− severely reduced or absent altogether.

Mentions: We added 800 nM of TSA to wildtype embryos between 16 and 24 hpf, after which embryos were fixed at 24 hpf and processed for dlx2-expression. We found qualitatively reduced numbers of dlx2-positive branchial arch precursors present in 800 nM TSA treated embryos (Fig. 4 A–D; Table 1). The 800 nM dose of TSA treatment had no effect on the numbers of dlx2-postive mandibular and hyoid arch-precursors present when compared to control DMSO-treated wildtype embryos. The selective effect of 800 nM TSA on neural crest branchial arch precursor specification in treated wildtype embryos, compared to mandibular and hyoid progenitors, was equivalent to that observed in hdac1b382 mutants.


Distinct functional and temporal requirements for zebrafish Hdac1 during neural crest-derived craniofacial and peripheral neuron development.

Ignatius MS, Unal Eroglu A, Malireddy S, Gallagher G, Nambiar RM, Henion PD - PLoS ONE (2013)

Treatment with the HDAC inhibitor TSA can reproduce the hdac1b382 mutant phenotype.A–d Lateral views of wild-type embryos treated with DMSO, 400 nM, 600 nM and 800 nM TSA from 16–24 hpf after which embryos were fixed and stained for dlx2 expression. A–D and A’–D’ Alcian blue stained 3.5 dpf wild-type embryos under different TSA treatment conditions, all embryos were treated between 16 hpf and 3.5 dpf after which embryos were fixed and then stained with alcian blue; A–A’ DMSO controls, B–B’ 400 nM TSA, C–C’ 600 nM TSA, D–D’ 800 nM TSA. A–D lateral view; A’–D’ ventral views. A’’–D’’ schematic with summary of craniofacial defects at different TSA treatment conditions. M, mandibular; H, hyoid; cb1-5, cerato-branchials 1-5; BA, branchial arches,+++ wild-type,++ reduced in size compared to wild-type,+severely reduced compared to wild-type, +/− severely reduced or absent altogether.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3646935&req=5

pone-0063218-g004: Treatment with the HDAC inhibitor TSA can reproduce the hdac1b382 mutant phenotype.A–d Lateral views of wild-type embryos treated with DMSO, 400 nM, 600 nM and 800 nM TSA from 16–24 hpf after which embryos were fixed and stained for dlx2 expression. A–D and A’–D’ Alcian blue stained 3.5 dpf wild-type embryos under different TSA treatment conditions, all embryos were treated between 16 hpf and 3.5 dpf after which embryos were fixed and then stained with alcian blue; A–A’ DMSO controls, B–B’ 400 nM TSA, C–C’ 600 nM TSA, D–D’ 800 nM TSA. A–D lateral view; A’–D’ ventral views. A’’–D’’ schematic with summary of craniofacial defects at different TSA treatment conditions. M, mandibular; H, hyoid; cb1-5, cerato-branchials 1-5; BA, branchial arches,+++ wild-type,++ reduced in size compared to wild-type,+severely reduced compared to wild-type, +/− severely reduced or absent altogether.
Mentions: We added 800 nM of TSA to wildtype embryos between 16 and 24 hpf, after which embryos were fixed at 24 hpf and processed for dlx2-expression. We found qualitatively reduced numbers of dlx2-positive branchial arch precursors present in 800 nM TSA treated embryos (Fig. 4 A–D; Table 1). The 800 nM dose of TSA treatment had no effect on the numbers of dlx2-postive mandibular and hyoid arch-precursors present when compared to control DMSO-treated wildtype embryos. The selective effect of 800 nM TSA on neural crest branchial arch precursor specification in treated wildtype embryos, compared to mandibular and hyoid progenitors, was equivalent to that observed in hdac1b382 mutants.

Bottom Line: In the peripheral nervous system, there is a disruption of enteric, DRG and sympathetic neuron differentiation in hdac1(b382) mutants compared to wildtype embryos.Sympathetic neuron precursors are specified in hdac1(b382) mutants and they undergo generic neuronal differentiation but fail to undergo noradrenergic differentiation.Using the HDAC inhibitor TSA, we isolated enzyme activity and temporal requirements for HDAC function that reproduce hdac1(b382) defects in craniofacial and sympathetic neuron development.

View Article: PubMed Central - PubMed

Affiliation: Molecular, Cellular and Developmental Biology Program, Ohio State University, Columbus, Ohio, United States of America.

ABSTRACT
The regulation of gene expression is accomplished by both genetic and epigenetic means and is required for the precise control of the development of the neural crest. In hdac1(b382) mutants, craniofacial cartilage development is defective in two distinct ways. First, fewer hoxb3a, dlx2 and dlx3-expressing posterior branchial arch precursors are specified and many of those that are consequently undergo apoptosis. Second, in contrast, normal numbers of progenitors are present in the anterior mandibular and hyoid arches, but chondrocyte precursors fail to terminally differentiate. In the peripheral nervous system, there is a disruption of enteric, DRG and sympathetic neuron differentiation in hdac1(b382) mutants compared to wildtype embryos. Specifically, enteric and DRG-precursors differentiate into neurons in the anterior gut and trunk respectively, while enteric and DRG neurons are rarely present in the posterior gut and tail. Sympathetic neuron precursors are specified in hdac1(b382) mutants and they undergo generic neuronal differentiation but fail to undergo noradrenergic differentiation. Using the HDAC inhibitor TSA, we isolated enzyme activity and temporal requirements for HDAC function that reproduce hdac1(b382) defects in craniofacial and sympathetic neuron development. Our study reveals distinct functional and temporal requirements for zebrafish hdac1 during neural crest-derived craniofacial and peripheral neuron development.

Show MeSH
Related in: MedlinePlus