Limits...
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.

Show MeSH

Related in: MedlinePlus

Craniofacial defects in hdac1b382 mutants.A–E alcian blue stained jaw elements in 5 dpf wild type A, C, E and hdac1b382 mutants B, D, F; A, B Ventral view of dissected craniofacial cartilages of wild-type and hdac1b382 mutant; C, D lateral view of head region in wild-type and hdac1b382 mutant; E,F, High magnification of the mandibular chondrocytes (arrows) in wild-type and hdac1b382 mutant; m, meckels; pq, platoquadrate; M, mandibular; ch, ceratohyal; hs, hyosymplectic; H, hyoid; cb1-5, ceratobrachials 1-5; BA, branchial arches.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3646935&req=5

pone-0063218-g001: Craniofacial defects in hdac1b382 mutants.A–E alcian blue stained jaw elements in 5 dpf wild type A, C, E and hdac1b382 mutants B, D, F; A, B Ventral view of dissected craniofacial cartilages of wild-type and hdac1b382 mutant; C, D lateral view of head region in wild-type and hdac1b382 mutant; E,F, High magnification of the mandibular chondrocytes (arrows) in wild-type and hdac1b382 mutant; m, meckels; pq, platoquadrate; M, mandibular; ch, ceratohyal; hs, hyosymplectic; H, hyoid; cb1-5, ceratobrachials 1-5; BA, branchial arches.

Mentions: In wildtype embryos at three days post fertilization (3 dpf), neural crest-derived cells of the pharyngeal arches differentiate and condense into distinct cartilage producing elements of the jaws detectable by alcian blue staining. Similarly, the precursor cells of the future neurocranium condense into clearly identifiable cartilaginous elements. In contrast, in hdac1b382 mutants at 3 dpf there is a complete lack of alcian blue stained-cartilage elements in the jaw [33]. Also, in hdac1b382 mutants the neurocranium cartilages are stained by alcian blue, however the neurocranium itself is reduced in size and the ethmoid plate elements fail to fuse at the midline as it does wildtype embryos [33]. Later, at 5 dpf, the mandibular and hyoid arches in hdac1b382 mutants are very faintly stained by alcian blue, compared to wildtype embryos, however these arch elements are not easily distinguishable and are drastically reduced in size (Fig. 1 A–D). Higher magnification resolution of chondrocytes in the mandibular and hyoid arches in wildtype embryos reveals well-defined, elongated cells. In contrast, in hdac1b382 mutants, few defined chondrocytes are visible and those that are observed are round in shape suggesting defects in terminal differentiation (Fig. 1 E, F). In hdac1b382 mutants, the different differentiated posterior branchial arch elements are altogether absent in alcian blue stained embryos (Fig. 1 A–D) at all stages examined. Thus, the disruption of hdac1 function in hdac1b382 mutants results in early defects in the establishment of posterior pharyngeal arch neural crest progenitor populations and a later defect in anterior arch morphogenesis and differentiation.


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)

Craniofacial defects in hdac1b382 mutants.A–E alcian blue stained jaw elements in 5 dpf wild type A, C, E and hdac1b382 mutants B, D, F; A, B Ventral view of dissected craniofacial cartilages of wild-type and hdac1b382 mutant; C, D lateral view of head region in wild-type and hdac1b382 mutant; E,F, High magnification of the mandibular chondrocytes (arrows) in wild-type and hdac1b382 mutant; m, meckels; pq, platoquadrate; M, mandibular; ch, ceratohyal; hs, hyosymplectic; H, hyoid; cb1-5, ceratobrachials 1-5; BA, branchial arches.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0063218-g001: Craniofacial defects in hdac1b382 mutants.A–E alcian blue stained jaw elements in 5 dpf wild type A, C, E and hdac1b382 mutants B, D, F; A, B Ventral view of dissected craniofacial cartilages of wild-type and hdac1b382 mutant; C, D lateral view of head region in wild-type and hdac1b382 mutant; E,F, High magnification of the mandibular chondrocytes (arrows) in wild-type and hdac1b382 mutant; m, meckels; pq, platoquadrate; M, mandibular; ch, ceratohyal; hs, hyosymplectic; H, hyoid; cb1-5, ceratobrachials 1-5; BA, branchial arches.
Mentions: In wildtype embryos at three days post fertilization (3 dpf), neural crest-derived cells of the pharyngeal arches differentiate and condense into distinct cartilage producing elements of the jaws detectable by alcian blue staining. Similarly, the precursor cells of the future neurocranium condense into clearly identifiable cartilaginous elements. In contrast, in hdac1b382 mutants at 3 dpf there is a complete lack of alcian blue stained-cartilage elements in the jaw [33]. Also, in hdac1b382 mutants the neurocranium cartilages are stained by alcian blue, however the neurocranium itself is reduced in size and the ethmoid plate elements fail to fuse at the midline as it does wildtype embryos [33]. Later, at 5 dpf, the mandibular and hyoid arches in hdac1b382 mutants are very faintly stained by alcian blue, compared to wildtype embryos, however these arch elements are not easily distinguishable and are drastically reduced in size (Fig. 1 A–D). Higher magnification resolution of chondrocytes in the mandibular and hyoid arches in wildtype embryos reveals well-defined, elongated cells. In contrast, in hdac1b382 mutants, few defined chondrocytes are visible and those that are observed are round in shape suggesting defects in terminal differentiation (Fig. 1 E, F). In hdac1b382 mutants, the different differentiated posterior branchial arch elements are altogether absent in alcian blue stained embryos (Fig. 1 A–D) at all stages examined. Thus, the disruption of hdac1 function in hdac1b382 mutants results in early defects in the establishment of posterior pharyngeal arch neural crest progenitor populations and a later defect in anterior arch morphogenesis and differentiation.

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