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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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Differential temporal requirements for HDAC function during craniofacial development.A–D and A’–D’ Wild-type embryos treated with TSA for 24 hpf at different stages of embryonic development. After treatment periods other than 48–72hpf, embryos were washed to remove TSA and then allowed to develop until 3.5 dpf. Embryos were fixed at 3.5 dpf and then stained with alcian blue. A–D lateral views, A’-D’ ventral views. A–A’ are DMSO-treated controls, B–B’ 16–40 hpf TSA-treated embryos, C–C’ 28–52 hpf TSA-treated embryos, D-D’ 48–72 hpf TSA-treated embryos. A’’-D’’ schematic with summary of craniofacial defects at different TSA treatment concentrations. 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-g005: Differential temporal requirements for HDAC function during craniofacial development.A–D and A’–D’ Wild-type embryos treated with TSA for 24 hpf at different stages of embryonic development. After treatment periods other than 48–72hpf, embryos were washed to remove TSA and then allowed to develop until 3.5 dpf. Embryos were fixed at 3.5 dpf and then stained with alcian blue. A–D lateral views, A’-D’ ventral views. A–A’ are DMSO-treated controls, B–B’ 16–40 hpf TSA-treated embryos, C–C’ 28–52 hpf TSA-treated embryos, D-D’ 48–72 hpf TSA-treated embryos. A’’-D’’ schematic with summary of craniofacial defects at different TSA treatment concentrations. 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: Treatment of wildtype embryos with 800 nM TSA for 24 h between 16 and 40 hpf resulted in alcian blue stained craniofacial cartilages with reduced sized mandibular, hyoid and branchial arch elements, although the shape of the jaw in TSA treated embryos was similar to control embryos (Fig. 5 B, B’, B”; Table 2). Later HDAC inhibition with 800 nM TSA between 28 and 52 hpf resulted in further reductions in the sizes of the mandibular, hyoid and branchial arch cartilages (Fig. 5 C, C’, C”; Table 2) compared to 16–40 hpf treatments. In addition to reductions in size of all craniofacial elements, in the branchial arches, inhibition of HDAC between 28–52 hpf resulted in the complete absence of alcian blue stained ceratobranchial (cb) cartilage elements cb3, cb4 and cb5 in 95%, 98% and 98% of treated embryos (n = 161), respectively. Finally, TSA treatment of wildtype embryos between 48–72 hpf (Fig. 5 D, D’, D”; Table 2) resulted in only minor reductions in the size of all craniofacial cartilage elements when compared to control embryos and also 16–40 and 28–52 hpf TSA treatments.


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)

Differential temporal requirements for HDAC function during craniofacial development.A–D and A’–D’ Wild-type embryos treated with TSA for 24 hpf at different stages of embryonic development. After treatment periods other than 48–72hpf, embryos were washed to remove TSA and then allowed to develop until 3.5 dpf. Embryos were fixed at 3.5 dpf and then stained with alcian blue. A–D lateral views, A’-D’ ventral views. A–A’ are DMSO-treated controls, B–B’ 16–40 hpf TSA-treated embryos, C–C’ 28–52 hpf TSA-treated embryos, D-D’ 48–72 hpf TSA-treated embryos. A’’-D’’ schematic with summary of craniofacial defects at different TSA treatment concentrations. 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.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3646935&req=5

pone-0063218-g005: Differential temporal requirements for HDAC function during craniofacial development.A–D and A’–D’ Wild-type embryos treated with TSA for 24 hpf at different stages of embryonic development. After treatment periods other than 48–72hpf, embryos were washed to remove TSA and then allowed to develop until 3.5 dpf. Embryos were fixed at 3.5 dpf and then stained with alcian blue. A–D lateral views, A’-D’ ventral views. A–A’ are DMSO-treated controls, B–B’ 16–40 hpf TSA-treated embryos, C–C’ 28–52 hpf TSA-treated embryos, D-D’ 48–72 hpf TSA-treated embryos. A’’-D’’ schematic with summary of craniofacial defects at different TSA treatment concentrations. 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: Treatment of wildtype embryos with 800 nM TSA for 24 h between 16 and 40 hpf resulted in alcian blue stained craniofacial cartilages with reduced sized mandibular, hyoid and branchial arch elements, although the shape of the jaw in TSA treated embryos was similar to control embryos (Fig. 5 B, B’, B”; Table 2). Later HDAC inhibition with 800 nM TSA between 28 and 52 hpf resulted in further reductions in the sizes of the mandibular, hyoid and branchial arch cartilages (Fig. 5 C, C’, C”; Table 2) compared to 16–40 hpf treatments. In addition to reductions in size of all craniofacial elements, in the branchial arches, inhibition of HDAC between 28–52 hpf resulted in the complete absence of alcian blue stained ceratobranchial (cb) cartilage elements cb3, cb4 and cb5 in 95%, 98% and 98% of treated embryos (n = 161), respectively. Finally, TSA treatment of wildtype embryos between 48–72 hpf (Fig. 5 D, D’, D”; Table 2) resulted in only minor reductions in the size of all craniofacial cartilage elements when compared to control embryos and also 16–40 and 28–52 hpf TSA treatments.

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