Developmental changes in phosphorylation of the transcription factor CREB in the embryonic murine palate

Weston, Wayde M.; Greene, Robert M.

doi:10.1002/jcp.1041640208

Cited by 12 publications

(4 citation statements)

References 43 publications

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“…26 The expression of CREB occurs at constant levels throughout the palatal development.26'27 Its predominant nuclear localization and a developmental increase in the phosphorylated form of CREB in palatal cells indicates that CREB-mediated gene transcription is likely regulated by changes in its phosphorylation rather than by changes in its expression.26 Results from our laboratory showed that the ontogeny of not only CREB but also several isoforms of CREM (activating and repressing) remained unchanged in the developing palate. Expression of ATF-1 and ATF-2, however, gradually decreased with the progression of development.27'28 Nuclear extracts of developing palate tissue contain CREB, CREM and an unidentified TF other than ATF-128 that bind to CRE forming a single protein-DNA complex.…”

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confidence: 94%

Alterations in protein kinase A signalling and cleft palate: a review

Reddy

2005

Hum Exp Toxicol

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Cyclic AMP is an important second messenger mediating the actions of many hormones and other ligands in a variety of cells. Cells of the developing organism are no exception. Once generated, it releases the catalytic subunit of protein kinase A (PKA) from the inhibitory influence of its regulatory subunit, which then migrates into the nucleus to phosphorylate and enhance the binding of relevant transcription factors to the promoter element CRE of genes involved in above cellular responses. This review summarizes the available data on the essential role of this pathway in embryonic development as well as the functionality, ontogeny and consequences of genetic and chemical disruption of this pathway in the developing orofacial structures, especially the secondary palate as influenced by the mycotoxin, secalonic acid D.

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confidence: 94%

Alterations in protein kinase A signalling and cleft palate: a review

Reddy

2005

Hum Exp Toxicol

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“…One very common birth defect is cleft palate, which occurs in 1:500 to 1:1000 live births (9). PKA activation and regulation have been previously described to play important roles in cAMP response element-binding protein (CREB) phosphorylation during palate formation (10). However, its function in relation to the CNC has not been elucidated.…”

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confidence: 99%

Neural Crest-Specific Loss of Prkar1a Causes Perinatal Lethality Resulting from Defects in Intramembranous Ossification

Jones¹,

Pringle²,

Yin³

et al. 2010

Molecular Endocrinology

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The cranial neural crest (CNC) undergoes complex molecular and morphological changes during embryogenesis in order to form the vertebrate skull, and nearly three quarters of all birth defects result from defects in craniofacial development. The molecular events leading to CNC differentiation have been extensively studied; however, the role of the cAMP-dependent protein kinase [protein kinase A (PKA)] during craniofacial development has only been described in palate formation. Here, we provide evidence that strict PKA regulation in postmigratory CNC cells is essential during craniofacial bone development. Selective inactivation of Prkar1a, a regulatory subunit of the PKA holoenzyme, in the CNC results in perinatal lethality caused by dysmorphic craniofacial development and subsequent asphyxiation. Additionally, aberrant differentiation of CNC mesenchymal cells results in anomalous intramembranous ossification characterized by formation of cartilaginous islands in some areas and osteolysis of bony trabeculae with fibrous connective tissue stabilization in others. Genetic interaction studies revealed that genetic reduction of the PKA catalytic subunit C(alpha) was able to rescue the phenotype, whereas reduction in Cbeta had no effect. Overall, these observations provide evidence of the essential role of proper regulation of PKA during the ossification of the bones of the skull. This knowledge may have implications for the understanding and treatment of craniofacial birth defects.

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“…The CREBBP-mediated transcription is likely regulated by changes in its phosphorylation rather than by changes in its expression. 32 Meanwhile, expression of ADCY9 was upregulated in the dental pulp stem cultures of NSCL/P patients. 21 Therefore, rs8049367 might contribute to DD and NSCL/P through its pleiotropic effects on CREBBP and ADCY9 , respectively.…”

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confidence: 99%

Genetic polymorphism of nonsyndromic cleft lip with or without cleft palate is associated with developmental dyslexia in Chinese school-aged populations

et al. 2016

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Developmental dyslexia (DD) is a neurodevelopment disorder characterized by reading disabilities without apparent etiologies. Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is a structural craniofacial malformation featured by isolated orofacial abnormalities. Despite substantial phenotypic differences, potential linkage between these two disorders has been suggested as prevalence of DD among NSCL/P patients was much higher than that in general populations. Previous neuroimaging studies observed impaired short-term memory in patients with DD and NSCL/P, respectively. Genetic factors have a fundamental role during neurodevelopment and craniofacial morphogenesis but there lacks of evidence to support the linkage between DD and NSCL/P at genetic level. A recent genome-wide association study in Chinese populations identified a number of genetic polymorphisms associated with NSCL/P. Herein, we selected three risk variants of NSCL/P namely rs8049367, rs4791774 and rs2235371, and performed association analysis with DD in a Chinese population consisting 631 elementary school-aged children with 288 dyslexic cases without NSCL/P and 343 healthy controls. After Bonferroni correction for multiple comparisons, the T allele of rs8049367 showed significant association with DD (OR=1.41, P=0.0085). It is an intergenic variant between CREBBP and ADCY9 located at 16p13.3. The CREBBP gene was reported to have an essential role during memory formation, although ADCY9 was involved in dental development. In future studies, understanding functional effects of rs8049367 on CERBBP and ADCY9 might contribute to explain underlying etiologies shared by DD and NSCL/P.

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Developmental changes in phosphorylation of the transcription factor CREB in the embryonic murine palate

Cited by 12 publications

References 43 publications

Alterations in protein kinase A signalling and cleft palate: a review

Alterations in protein kinase A signalling and cleft palate: a review

Neural Crest-Specific Loss of Prkar1a Causes Perinatal Lethality Resulting from Defects in Intramembranous Ossification

Genetic polymorphism of nonsyndromic cleft lip with or without cleft palate is associated with developmental dyslexia in Chinese school-aged populations

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