Abstract:
:Spinal cord regenerative ability is lost with development, but the mechanisms underlying this loss are still poorly understood. In chick embryos, effective regeneration does not occur after E13, when spinal cord injury induces extensive apoptotic response and tissue damage. As initial experiments showed that treatment with a calcium chelator after spinal cord injury reduced apoptosis and cavitation, we hypothesized that developmentally regulated mediators of calcium-dependent processes in secondary injury response may contribute to loss of regenerative ability. To this purpose we screened for such changes in chick spinal cords at stages of development permissive (E11) and non-permissive (E15) for regeneration. Among the developmentally regulated calcium-dependent proteins identified was PAD3, a member of the peptidylarginine deiminase (PAD) enzyme family that converts protein arginine residues to citrulline, a process known as deimination or citrullination. This post-translational modification has not been previously associated with response to injury. Following injury, PAD3 up-regulation was greater in spinal cords injured at E15 than at E11. Consistent with these differences in gene expression, deimination was more extensive at the non-regenerating stage, E15, both in the gray and white matter. As deimination paralleled the extent of apoptosis, we investigated the effect of blocking PAD activity on cell death and deiminated-histone 3, one of the PAD targets we identified by mass-spectrometry analysis of spinal cord deiminated proteins. Treatment with the PAD inhibitor, Cl-amidine, reduced the abundance of deiminated-histone 3, consistent with inhibition of PAD activity, and significantly reduced apoptosis and tissue loss following injury at E15. Altogether, our findings identify PADs and deimination as developmentally regulated modulators of secondary injury response, and suggest that PADs might be valuable therapeutic targets for spinal cord injury.
journal_name
Dev Bioljournal_title
Developmental biologyauthors
Lange S,Gögel S,Leung KY,Vernay B,Nicholas AP,Causey CP,Thompson PR,Greene ND,Ferretti Pdoi
10.1016/j.ydbio.2011.04.015subject
Has Abstractpub_date
2011-07-15 00:00:00pages
205-14issue
2eissn
0012-1606issn
1095-564Xpii
S0012-1606(11)00247-8journal_volume
355pub_type
杂志文章abstract::Polychaete annelids and arthropods are both segmented protostome invertebrates. To investigate whether the segmented body plan of these two phyla share a common molecular ground pattern, we report the developmental expression of orthologues of the arthropod segment polarity genes engrailed (en), hedgehog (hh), and win...
journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1016/j.ydbio.2005.10.025
更新日期:2006-01-01 00:00:00
abstract::The relationship between ascorbic acid concentration and cellular transport mechanisms was studied in chicken embryos (Gallus gallus domesticus). Unincubated (Day 0) fertile eggs did not contain detectable levels of ascorbic acid as assayed by high performance liquid chromatography with electrochemical detection. Howe...
journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1016/0012-1606(90)90298-w
更新日期:1990-06-01 00:00:00
abstract::Mutations at the Drosophila melanogaster locus female sterile (1) homeotic (fs(1)h) result in segmental abnormalities including missing organs and homeotic transformations in the progeny of mutant mothers. Homeotic transformations are enhanced when the zygotes carry one of several third chromosome mutations, specifica...
journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1016/0012-1606(86)90392-1
更新日期:1986-03-01 00:00:00
abstract::Insulin-like growth factor-1 (IGF-1) is believed to play a role in the regulation of brain growth. The identity of cells responsible for its synthesis in the immature brain, however, has not been established. To identify potential sites of IGF-1 synthesis, in situ hybridization has been utilized to localize IGF-1 mRNA...
journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1016/s0012-1606(05)80021-1
更新日期:1991-09-01 00:00:00
abstract::John W. Saunders, Jr. made seminal discoveries unveiling how chick embryos develop their limbs. He discovered the apical ectodermal ridge (AER), the zone of polarizing activity (ZPA), and the domains of interdigital cell death within the developing limb and determined their function through experimental analysis. Thes...
journal_title:Developmental biology
pub_type: 杂志文章,评审
doi:10.1016/j.ydbio.2016.11.005
更新日期:2017-09-15 00:00:00
abstract::Wnt signaling pathways have been demonstrated to play important roles in controlling tissue patterning and cell proliferation. In the gastrointestinal tract, mutations that lead to activation of the canonical Wnt pathway through beta-catenin result in familial and sporadic colon cancers. The downstream transcription f...
journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1016/s0012-1606(03)00185-4
更新日期:2003-07-15 00:00:00
abstract::In the deuterostomes and ecdysozoans that have been studied (e.g. chordates and insects), neural fate specification relies on signaling from surrounding cells. However, very little is known about mechanisms of neural specification in the third major bilaterian clade, spiralians. Using blastomere isolation in the annel...
journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1016/j.ydbio.2017.09.022
更新日期:2017-11-15 00:00:00
abstract::We utilized a strain of mice, derived from a radiation mutagenesis experiment and carrying an activity-attenuated allele of the X-linked enzyme glucose-6-phosphate dehydrogenase (G6PD), to analyze the development of the cell lineage leading to cerebellar Purkinje neurons. Due to random X inactivation during early embr...
journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1006/dbio.1996.0083
更新日期:1996-03-15 00:00:00
abstract::Eight series of mouse chimeras were produced by aggregating 8-cell embryos that differed at the Gpi-1s locus, encoding glucose phosphate isomerase (GPI-1). Chimeric blastocysts (Gpi-1sa/Gpi-1sa <--> Gpi-1sb/Gpi-1sb) were transferred to pseudopregnant females, which produced only GPI-1C enzyme. Quantitative electrophor...
journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1006/dbio.1995.1062
更新日期:1995-03-01 00:00:00
abstract::Coordinated contraction of the heart is essential for survival and is regulated by the cardiac conduction system. Contraction of ventricular myocytes is controlled by the terminal part of the conduction system known as the Purkinje fiber network. Lineage analyses in chickens and mice have established that the Purkinje...
journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1016/j.ydbio.2014.07.008
更新日期:2014-09-15 00:00:00
abstract::The uterus undergoes a series of dramatic changes in response to an implanting conceptus that, in some mammalian species, includes differentiation of the endometrial stroma into decidual tissue. This process, called decidualization, can be induced artificially in rodents indicating that the conceptus may not be essent...
journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1016/j.ydbio.2006.03.006
更新日期:2006-06-15 00:00:00
abstract::Initiation of the development of the anterior-posterior axis in the mouse embryo has been thought to take place only when the anterior visceral endoderm (AVE) emerges and starts its asymmetric migration. However, expression of Lefty1, a marker of the AVE, was recently found to initiate before embryo implantation. This...
journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1016/j.ydbio.2007.06.020
更新日期:2007-09-01 00:00:00
abstract::Polycomb group (PcG) proteins are best known for their role in maintaining stable, mitotically heritable silencing of the homeotic (HOX) genes during development. In addition to loss of homeotic gene silencing, some PcG mutants also have small imaginal discs. These include mutations in E(z), Su(z)12, esc and escl, whi...
journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1016/j.ydbio.2013.03.011
更新日期:2013-08-01 00:00:00
abstract::Cleft palate is one of the most common craniofacial congenital defects in humans. It is associated with multiple genetic and environmental risk factors, including mutations in the genes encoding signaling molecules in the sonic hedgehog (Shh) pathway, which are risk factors for cleft palate in both humans and mice. Ho...
journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1016/j.ydbio.2018.07.003
更新日期:2018-09-01 00:00:00
abstract::Septins are guanosine triphosphate-binding proteins that are evolutionally conserved in all eukaryotes other than plants. They function as multimeric complexes that interact with membrane lipids, actomyosin, and microtubules. Based on these interactions, septins play essential roles in the morphogenesis and physiologi...
journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1016/j.ydbio.2016.09.012
更新日期:2016-11-15 00:00:00
abstract::I report on the synthesis of fibronectin in the developing chick Müllerian duct mesenchymal cells. Before the differentiation of female chick Müllerian duct, the amount of fibronectin in the cells of the right duct is 44% lower than in the left duct. While after differentiation, the amount of fibronectin in the right ...
journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1016/0012-1606(90)90047-m
更新日期:1990-07-01 00:00:00
abstract::Mutations in the NF1 gene may cause developmental abnormalities and the formation of a variety of tumors of neural crest origin in humans. The NF1 gene codes for a large protein, neurofibromin (nf), which is structurally and functionally related to yeast and human ras-GTPase-activating proteins (ras-GAPs). Recently, t...
journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1006/dbio.1994.1052
更新日期:1994-02-01 00:00:00
abstract::The sea urchin sperm receptor isolated from the eggs of Strongylocentrotus purpuratus is a high molecular weight proteoglycan-like molecule. Previous studies in our laboratory suggested that the sperm receptor has two functional components, glycosaminoglycan chains that are responsible for sperm binding and polypeptid...
journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1016/0012-1606(86)90088-6
更新日期:1986-11-01 00:00:00
abstract::Recent results have demonstrated the occurrence of mRNA cap methylation in the sea urchin embryo following fertilization. It has been suggested that this methylation event is responsible for the translational activation of maternal histone mRNAs in these embryos. We have used aphidicolin, an effective inhibitor of bot...
journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1016/0012-1606(87)90161-8
更新日期:1987-05-01 00:00:00
abstract::In the present study, we have investigated the role of tyrosine kinase activity during early retinal development in Xenopus laevis. The protein tyrosine kinase (PTK) inhibitors lavendustin A and genistein were used to determine the possible role of tyrosine kinase activity during retinal development in vivo and in vit...
journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1016/j.ydbio.2003.10.006
更新日期:2004-02-01 00:00:00
abstract::The Toll signaling pathway functions in several Drosophila processes, including dorsal-ventral pattern formation and the immune response. Here, we demonstrate that this pathway is required in the epidermis for proper muscle development. Previously, we showed that the zygotic Toll protein is necessary for normal muscle...
journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1006/dbio.1998.8915
更新日期:1998-07-01 00:00:00
abstract::The Mix/Bix family of paired-like homeobox genes encode evolutionarily conserved, sequence specific, DNA-binding transcription factors that have been implicated in the co-ordination of gene expression, axis formation and cell fate determination during gastrulation in vertebrates. When mutated, these genes give rise to...
journal_title:Developmental biology
pub_type: 杂志文章,评审
doi:10.1016/j.ydbio.2012.04.033
更新日期:2012-07-15 00:00:00
abstract::Actin-related protein 5 (ARP5) is a conserved subunit of the INO80 chromatin-remodeling complex in yeast and mammals. We have characterized the expression and subcellular distribution of Arabidopsis thaliana ARP5 and explored its role in the epigenetic control of multicellular development and DNA repair. ARP5-specific...
journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1016/j.ydbio.2009.08.006
更新日期:2009-11-01 00:00:00
abstract::The mammary gland (MG) is a unique organ responsible for milk synthesis, secretion, and involution to prepare the gland for subsequent lactation. The mammary epithelial cells (MECs), which are the milk synthesizing units of the MG, proliferate, differentiate, undergo apoptosis and regenerate following a cyclic pathway...
journal_title:Developmental biology
pub_type: 杂志文章,评审
doi:10.1016/j.ydbio.2018.11.002
更新日期:2019-01-15 00:00:00
abstract::The relationship between cellular position and growth control has been studied in cultures of dissociated fragments of mouse limb bud cells. Using cells derived from various positions along the anterior-posterior axis of the limb bud we have developed culture conditions that optimize growth of positionally isolated ce...
journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1016/0012-1606(92)90208-x
更新日期:1992-05-01 00:00:00
abstract::The dopaminergic neurons of the basal ganglia play critical roles in CNS function and human disease, but specification of dopamine neuron phenotype is poorly understood in vertebrates. We performed an in vivo screen in zebrafish to identify dopaminergic neuron enhancers, in order to facilitate studies on the specifica...
journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1016/j.ydbio.2011.01.023
更新日期:2011-04-15 00:00:00
abstract::We have previously reported the detection of cAMP waves within monolayers of aggregating Dictyostelium discoideum cells (K. J. Tomchik and P.N. Devreotes, 1981, Science 212, 443-446). The computer-assisted analysis presented here of the fluorographic images of the cAMP waves reveals (1) all the waves have a consistent...
journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1016/0012-1606(83)90178-1
更新日期:1983-04-01 00:00:00
abstract::Human MusTRD1alpha1 was isolated as a result of its ability to bind a critical element within the Troponin I slow upstream enhancer (TnIslow USE) and was predicted to be a regulator of slow fiber-specific genes. To test this hypothesis in vivo, we generated transgenic mice expressing hMusTRD1alpha1 in skeletal muscle....
journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1016/j.ydbio.2006.01.019
更新日期:2006-05-01 00:00:00
abstract::Cell signaling pathways, such as Wnt, Hedgehog (Hh), Notch, and Hippo, are essential for embryogenesis, organogenesis, and tissue homeostasis. In this study, we analyzed 415 genes involved in these pathways in the allotetraploid frog, Xenopus laevis. Most genes are retained in two subgenomes called L and S (193 homeol...
journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1016/j.ydbio.2016.12.006
更新日期:2017-06-15 00:00:00
abstract::In the vertebrate head, crucial parts of the sense organs and sensory ganglia develop from special regions, the cranial placodes. Despite their cellular and functional diversity, they arise from a common field of multipotent progenitors and acquire distinct identity later under the influence of local signalling. Here ...
journal_title:Developmental biology
pub_type: 杂志文章,评审
doi:10.1016/j.ydbio.2012.06.028
更新日期:2012-10-01 00:00:00