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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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Related in: MedlinePlus

Hdac1 levels are severely reduced in hdac1b382 mutants.Western blots for total Hdac1 from wild-type and hdac1b382 (labeled hdac1col) mutants at 1, 3, 5 and 7 dpf. ß-actin was used as a loading control.
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pone-0063218-g008: Hdac1 levels are severely reduced in hdac1b382 mutants.Western blots for total Hdac1 from wild-type and hdac1b382 (labeled hdac1col) mutants at 1, 3, 5 and 7 dpf. ß-actin was used as a loading control.

Mentions: A feature of the hdac1b382 mutant phenotype is the progressive perturbation of the development of multiple tissues over time culminating with death by 7 to 8 dpf. While there are clear gene expression patterning defects as early as gastrulation, obvious visible differences between mutants and wild-type embryos are first observed at 27 hpf highlighted by pigmentation abnormalities and then at 48 hpf by cardiac, pectoral fin and jaw defects [33]. The progressive elaboration of developmental defects in mutant embryos could be due to cumulative effects of constant relative reduced levels of Hdac1 protein or potentially to a progressive reduction in relative Hdac1 levels. We therefore analyzed the levels of Hdac1 protein in wildtype and mutant embryos at 1, 3, 5 and 7 dpf by Western analysis (Fig. 8). We find that Hdac1 protein levels are reduced in mutants when compared to wild-type embryos at all time points analyzed. Further, as development progresses, whereas Hdac1 levels in wildtype embryos and larvae increase, relative Hdac1 levels decrease in mutant embryos such that by 7 dpf, Hdac1 protein is not readily detectable in mutant embryos. These results raise the possibility that the progressive nature of the hdac1b382 mutant phenotype results from decreasing relative levels of Hdac1 protein as development proceeds, possibly due to an autoregulatory mechanism controlling Hdac1 expression or due to the degradation of maternally supplied mRNA/protein over developmental time.


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)

Hdac1 levels are severely reduced in hdac1b382 mutants.Western blots for total Hdac1 from wild-type and hdac1b382 (labeled hdac1col) mutants at 1, 3, 5 and 7 dpf. ß-actin was used as a loading control.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0063218-g008: Hdac1 levels are severely reduced in hdac1b382 mutants.Western blots for total Hdac1 from wild-type and hdac1b382 (labeled hdac1col) mutants at 1, 3, 5 and 7 dpf. ß-actin was used as a loading control.
Mentions: A feature of the hdac1b382 mutant phenotype is the progressive perturbation of the development of multiple tissues over time culminating with death by 7 to 8 dpf. While there are clear gene expression patterning defects as early as gastrulation, obvious visible differences between mutants and wild-type embryos are first observed at 27 hpf highlighted by pigmentation abnormalities and then at 48 hpf by cardiac, pectoral fin and jaw defects [33]. The progressive elaboration of developmental defects in mutant embryos could be due to cumulative effects of constant relative reduced levels of Hdac1 protein or potentially to a progressive reduction in relative Hdac1 levels. We therefore analyzed the levels of Hdac1 protein in wildtype and mutant embryos at 1, 3, 5 and 7 dpf by Western analysis (Fig. 8). We find that Hdac1 protein levels are reduced in mutants when compared to wild-type embryos at all time points analyzed. Further, as development progresses, whereas Hdac1 levels in wildtype embryos and larvae increase, relative Hdac1 levels decrease in mutant embryos such that by 7 dpf, Hdac1 protein is not readily detectable in mutant embryos. These results raise the possibility that the progressive nature of the hdac1b382 mutant phenotype results from decreasing relative levels of Hdac1 protein as development proceeds, possibly due to an autoregulatory mechanism controlling Hdac1 expression or due to the degradation of maternally supplied mRNA/protein over developmental time.

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