DeltaNp73 regulates neuronal survival in vivo

Tissir, Fadel; Ravni, Aurélia; Achouri, Younès; Riethmacher, Dieter; Meyer, Gundela; Goffinet, André M.

doi:10.1073/pnas.0903191106

Cited by 141 publications

(226 citation statements)

References 43 publications

(62 reference statements)

Supporting

Mentioning

207

Contrasting

Unclassified

Order By: Relevance

“…Other p73 mRNA variants (aTAp73 and ∆Np73) encode smaller or truncated proteins which lack at least one domain (i.e. aTAp73 does not contain TA domain) [7]. Although there are numerous studies related to the p53 status in CRC, the reports on the expression of p73 gene and protein in this type of cancer are scarce and unequivocal [8][9][10].…”

mentioning

confidence: 98%

Decreased expression of p73 in colorectal cancer

Kotulak

Wrońska

Godlewski

et al. 2016

Folia Histochem Cytobiol.

View full text Add to dashboard Cite

Introduction. The colorectal cancer (CRC) is one of the most frequent cancer in Poland and worldwide. This disease is characterized by distinct genetic alterations. p73 belongs to the p53 gene family; however, its role in the pathogenesis of CRC has not been completely understood. p73 gene encodes several mRNA variants and protein isoforms with its longest and fully functional p73a (mRNA) and TAp73a (protein) isoform. The aim of the study was to investigate p73 gene expression at the mRNA (p73a) and protein (TAp73a) levels in CRC. Material and methods. Small sections of the CRC tumor tissue and macroscopically unchanged colon mucosa and submucosa from the dissection margin were collected from 23 patients diagnosed with CRC. p73 mRNA levels were measured by Real-time PCR (QPCR) method and the expression level of TAp73a protein was assessed by Western blotting (WB) and immunohistochemical (IHC) staining. Results. We found a 37% decrease in the level of p73a mRNA in neoplastically changed (tumor) compared with unchanged normal colon tissue from the surgical margin (p = 0.041). No correlations were found between mRNA levels in cancer tissue and clinical-pathological parameters. The semi-quantification of TAp73a protein revealed lower and higher TAp73a protein contents in 11/23 and 12/23 of tumor samples, respectively, when compared with the median value of TAp73a protein in normal colon tissue (p = 0.61). The level of TAp73a protein level was 5 times lower in poorly differentiated cancer cells (G3) in comparison to moderately differentiated ones (G2; p = 0.02). No statistically significant correlations were observed between the level of the TAp73a protein and clinical-pathological patients' characteristics. The IHC analysis of TAp73a protein presence in CRC samples showed decreased immunoreactivity when compared with matched sections of the unchanged colon wall in 4/9 patients, similar intensity of the IHC reaction in 4/9 patients and increased immunoreactivity in 1/9 patients. The TAp73a protein was localized mainly in the cytoplasm of the cancer cells. No statistically significant correlations between IHC results and clinical-pathological features of the patients were found. Conclusions. The obtained results suggest that the p73 gene may play a role as a tumor suppressor in the CRC progression.

show abstract

mentioning

confidence: 98%

Decreased expression of p73 in colorectal cancer

Kotulak

Wrońska

Godlewski

et al. 2016

Folia Histochem Cytobiol.

View full text Add to dashboard Cite

show abstract

“…In the mouse, the majority (98%) of p73-positive CR cells co-express reelin, whereas only 75% of reelin-positive CR cells co-express p73 (Tissir et al 2009). By contrast, in human fetuses, virtually all cells in the neocortical MZ with the typical CR cell morphology co-express reelin and p73 (Meyer et al 2002;CabreraSocorro et al 2007).…”

Section: The Importance Of Cajal-retzius Cells and Reelin For Corticamentioning

confidence: 99%

“…Cajal-Retzius cells provide an interesting example for programmed cell death. Although it has sometimes been argued that CR cells do not die but become diluted in an expanding cortex, there is direct evidence for degeneration and death of CR cells in human and rodents (Derer & Derer, 1990;Meyer & Gonzalez-Hernandez, 1993;Meyer et al 2002;Tissir et al 2009). In human, they disappear from 23 GW onward, in mice by the end of the first postnatal week.…”

Section: The Importance Of Cajal-retzius Cells and Reelin For Corticamentioning

confidence: 99%

“…The tumour protein p73, widely used as a marker molecule for CR cells, plays a pivotal role in the life and death of a neuron (Kaghad et al 1997;Pozniak et al 2002;Jacobs et al 2006). In the developing brain, expression of p73 is restricted to CR cells, the cortical hem and the choroid plexuses (Yang et al 2000;Meyer et al 2004;Tissir et al 2009). …”

Section: The Importance Of Cajal-retzius Cells and Reelin For Corticamentioning

confidence: 99%

See 1 more Smart Citation

Building a human cortex: the evolutionary differentiation of Cajal‐Retzius cells and the cortical hem

Meyer

2010

Journal of Anatomy

Self Cite

102

View full text Add to dashboard Cite

Cajal-Retzius (CR) cells are the most significant source of reelin, an extracellular matrix glycoprotein essential for cortical development. Strategically located in the marginal zone, CR cells control radial migration and laminar positioning of pyramidal neurons of the cortical plate. They degenerate and undergo cell death when cortical migration is completed. In human cortex development, reelin-expressing CR cells are already present in the early preplate, and continue to increase in number after the appearance of the cortical plate. In the course of the first half of gestation, the reelin signal in the marginal zone undergoes a huge amplification in parallel with the growth of the cortical plate and the expansion of the cortical surface. A significant source of CR cells is the cortical hem, a putative signalling centre at the interface of the prospective hippocampus and the choroid plexus. Hem-derived CR cells co-express reelin and p73, a transcription factor of the p53-family. They form the predominant CR cell population of the human neocortex. Characteristically, CR cells express the anti-apoptotic isoform DeltaNp73 which may be responsible for the protracted lifespan of human CR cells and the morphological differentiation of their axonal plexus. This dense fibre plexus, absent in lower mammals, amplifies the reelin-signal and establishes a physical boundary between the cortical plate and the marginal zone. In this review, we analyze the multiple sources of reelin ⁄ p73 positive CR cells at the interface of various telencephalic centres and the choroid plexus of the lateral ventricles. Additional populations of CR cells may derive from the thalamic eminence in the ventral thalamus and from the strionuclear neuroepithelium, or 'amygdalar hem'. Comparative studies in a variety of species indicate that the cortical hem is the main origin of CR cells destined for the neocortex, and is most highly developed in the human brain. The close association between cortical hem and choroid plexus suggests a concerted role in the evolutionary increase of CR cells, amplification of the reelin signal in the marginal zone, and cortical expansion.

show abstract

“…94 Moreover, a p73 N-terminal truncated version (∆Np73) has been shown to promote survival of neurons upon growth factor withdrawal. 95 …”

Section: Teadsmentioning

confidence: 99%