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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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Neural crest-derived posterior branchial arch progenitor specification is defective in hdac1b382 mutants.A, C, E, G, I, K wild-type embryos, B, D, F, H, J, L hdac1b382 mutants. A, B Dorsal view of embryos at 25 hpf with dlx2 expression labeling the mandibular, hyoid and branchial arch precursor populations. C, D Lateral views of the head region at 25 hpf of crestin expression in the head region, black arrowheads indicate branchial arch populations. E, F, Lateral views of the head region at 25 hpf of hoxb3a expression in the hind-brain and branchial arch precursors. G, H, Lateral views of the head region at 96 hpf of col2a1 expression in mandibular, hyoid and branchial arches. I, J, Lateral views of the head region at 56 hpf of TUNEL-positive staining in the head and jaw regions. K, L, Side views of the head region at 32 hpf with tbx1 expression highlighting the endodermal pouches. M, mandibular; H, hyoid; BA, branchial arches.
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pone-0063218-g003: Neural crest-derived posterior branchial arch progenitor specification is defective in hdac1b382 mutants.A, C, E, G, I, K wild-type embryos, B, D, F, H, J, L hdac1b382 mutants. A, B Dorsal view of embryos at 25 hpf with dlx2 expression labeling the mandibular, hyoid and branchial arch precursor populations. C, D Lateral views of the head region at 25 hpf of crestin expression in the head region, black arrowheads indicate branchial arch populations. E, F, Lateral views of the head region at 25 hpf of hoxb3a expression in the hind-brain and branchial arch precursors. G, H, Lateral views of the head region at 96 hpf of col2a1 expression in mandibular, hyoid and branchial arches. I, J, Lateral views of the head region at 56 hpf of TUNEL-positive staining in the head and jaw regions. K, L, Side views of the head region at 32 hpf with tbx1 expression highlighting the endodermal pouches. M, mandibular; H, hyoid; BA, branchial arches.

Mentions: At 48 hpf, the pharyngeal skeleton has a distinct dorso-ventral dimension as a result of the ventral migration of neural crest-derived cells into the pharyngeal pouches [57]. Migrating pharyngeal arch neural crest cells express dlx2. In the mandibular and hyoid arch, while qualitatively there are equivalent numbers of migrating neural crest cells in hdac1b382 mutant and wildtype embryos, cranial neural crest morphogenesis is defective in mutant embryos (Fig. 2 A, B). Consistent with defects in morphogenesis, the number of dlx3-positive cranial neural crest cells localized to the ventral most jaw elements, are significantly reduced in hdac1b382 mutants (Fig. 2 C, D). We next analyzed the expression of col2a1 which is a major collagen produced in the differentiating pharyngeal arch elements [15], [58]. In wild-type embryos by 68 hpf, col2a1 is robustly expressed by all elements of the pharyngeal arches. In contrast, in hdac1b382 mutants, there is a delay in the expression of col2a1 by a day in the mandibular and hyoid arches (Fig. 2 E, F; Fig. 3 G, H). Further, there is a distinct patterning defect whereby the elements of the hyoid arch from both sides of the head fail to meet ventrally close to the middle of the head. There are also defects in the size and formation of the mandibular arch elements (data not shown).


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)

Neural crest-derived posterior branchial arch progenitor specification is defective in hdac1b382 mutants.A, C, E, G, I, K wild-type embryos, B, D, F, H, J, L hdac1b382 mutants. A, B Dorsal view of embryos at 25 hpf with dlx2 expression labeling the mandibular, hyoid and branchial arch precursor populations. C, D Lateral views of the head region at 25 hpf of crestin expression in the head region, black arrowheads indicate branchial arch populations. E, F, Lateral views of the head region at 25 hpf of hoxb3a expression in the hind-brain and branchial arch precursors. G, H, Lateral views of the head region at 96 hpf of col2a1 expression in mandibular, hyoid and branchial arches. I, J, Lateral views of the head region at 56 hpf of TUNEL-positive staining in the head and jaw regions. K, L, Side views of the head region at 32 hpf with tbx1 expression highlighting the endodermal pouches. M, mandibular; H, hyoid; BA, branchial arches.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3646935&req=5

pone-0063218-g003: Neural crest-derived posterior branchial arch progenitor specification is defective in hdac1b382 mutants.A, C, E, G, I, K wild-type embryos, B, D, F, H, J, L hdac1b382 mutants. A, B Dorsal view of embryos at 25 hpf with dlx2 expression labeling the mandibular, hyoid and branchial arch precursor populations. C, D Lateral views of the head region at 25 hpf of crestin expression in the head region, black arrowheads indicate branchial arch populations. E, F, Lateral views of the head region at 25 hpf of hoxb3a expression in the hind-brain and branchial arch precursors. G, H, Lateral views of the head region at 96 hpf of col2a1 expression in mandibular, hyoid and branchial arches. I, J, Lateral views of the head region at 56 hpf of TUNEL-positive staining in the head and jaw regions. K, L, Side views of the head region at 32 hpf with tbx1 expression highlighting the endodermal pouches. M, mandibular; H, hyoid; BA, branchial arches.
Mentions: At 48 hpf, the pharyngeal skeleton has a distinct dorso-ventral dimension as a result of the ventral migration of neural crest-derived cells into the pharyngeal pouches [57]. Migrating pharyngeal arch neural crest cells express dlx2. In the mandibular and hyoid arch, while qualitatively there are equivalent numbers of migrating neural crest cells in hdac1b382 mutant and wildtype embryos, cranial neural crest morphogenesis is defective in mutant embryos (Fig. 2 A, B). Consistent with defects in morphogenesis, the number of dlx3-positive cranial neural crest cells localized to the ventral most jaw elements, are significantly reduced in hdac1b382 mutants (Fig. 2 C, D). We next analyzed the expression of col2a1 which is a major collagen produced in the differentiating pharyngeal arch elements [15], [58]. In wild-type embryos by 68 hpf, col2a1 is robustly expressed by all elements of the pharyngeal arches. In contrast, in hdac1b382 mutants, there is a delay in the expression of col2a1 by a day in the mandibular and hyoid arches (Fig. 2 E, F; Fig. 3 G, H). Further, there is a distinct patterning defect whereby the elements of the hyoid arch from both sides of the head fail to meet ventrally close to the middle of the head. There are also defects in the size and formation of the mandibular arch elements (data not shown).

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