Developmental Roles of p73 in Cajal-Retzius Cells and Cortical Patterning

Meyer, Gundela; Socorro, Alfredo Cabrera; Garcia, Carlos Gustavo Perez; Millán, Luis Martínez; Walker, Nancy M.; Caput, Daniel

doi:10.1523/jneurosci.3060-04.2004

Cited by 120 publications

(145 citation statements)

References 64 publications

(67 reference statements)

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“…Because our data suggested a possible role of meningeally expressed SDF1 as a chemoattractant for Cajal-Retzius cells, we wanted to readdress this question. Using p73 as an unambiguous marker for Cajal-Retzius cells (Meyer et al, 2004), we found the expected localization of Cajal-Retzius cells in control animals, in the marginal zone, closely abutting the meninges (Fig. 5a,b).…”

Section: Sdf1 Signaling Regulates Laminar Position Of Cajal-retzius Cmentioning

confidence: 66%

Stromal-Derived Factor-1 (CXCL12) Regulates Laminar Position of Cajal-Retzius Cells in Normal and Dysplastic Brains

Paredes

Li²,

Berger³

et al. 2006

J. Neurosci.

119

111

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Normal brain development requires a series of highly complex and interrelated steps. This process presents many opportunities for errors to occur, which could result in developmental defects in the brain, clinically referred to as malformations of cortical development. The marginal zone and Cajal-Retzius cells are key players in cortical development and are established early, yet there is little understanding of the factors resulting in the disruption of the marginal zone in many types of cortical malformation syndromes. We showed previously that treatment with methylazoxymethanol in rats causes marginal zone dysplasia with displacement of Cajal-Retzius cells to deeper cortical layers. Here we establish that loss of activity of the chemokine stromal-derived factor-1 (SDF1) (CXCL12), which is expressed by the leptomeninges, is necessary and sufficient to cause marginal zone disorganization in this widely used teratogenic animal model. We also found that mice with mutations in the main receptor for SDF1 (CXCR4) have Cajal-Retzius cells displaced to deeper cortical layers. Furthermore, by inhibiting SDF1 signaling in utero by intraventricular injection of a receptor antagonist, we establish that SDF1 signaling is required for the maintenance of Cajal-Retzius cell position in the marginal zone during normal cortical development. Our data imply that cortical layering is not a static process, but rather requires input from locally produced molecular cues for maintenance, and that complex syndromes of cortical malformation as a result of environmental insults may still be amenable to explanation by interruption of specific molecular signaling pathways.

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Section: Sdf1 Signaling Regulates Laminar Position Of Cajal-retzius Cmentioning

confidence: 66%

Stromal-Derived Factor-1 (CXCL12) Regulates Laminar Position of Cajal-Retzius Cells in Normal and Dysplastic Brains

Paredes

Li²,

Berger³

et al. 2006

J. Neurosci.

119

111

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“…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%

“…p73 is a complex protein that appears in two main isoforms with opposite functions. The transactivation-competent TA-isoforms have pro-apoptotic activities and predominate in the cortical hem (Yang et al 2000;Meyer et al 2004). In turn, the N-truncated (DeltaNp73) isoforms are able to bind to DNA and to form dimers with TAp73, as well as with p53 and p63, and behave as dominant negative, anti-apoptotic factors (Yang et al 2000;Grob et al 2001;Pozniak et al 2002;Jacobs et al 2006).…”

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

confidence: 99%

“…In turn, the N-truncated (DeltaNp73) isoforms are able to bind to DNA and to form dimers with TAp73, as well as with p53 and p63, and behave as dominant negative, anti-apoptotic factors (Yang et al 2000;Grob et al 2001;Pozniak et al 2002;Jacobs et al 2006). Expression of DeltaNp73 is characteristic of the CR cell population derived from the cortical hem (Yang et al 2000;Meyer et al 2002Meyer et al , 2004Tissir et al 2009). …”

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

confidence: 99%

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

Meyer

2010

Journal of Anatomy

102

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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.

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“…The role of p73 is significant in the central nervous system development, since the p73 knock-out mice present hippocampal dysgenesis, cortical hypoplasia and hydrocephalus, meaning that p73 plays an important role in the different parameters regulating brain development [19]. The transactivating isoforms of p73 (TAp73) are similar to p53 acting as transcription factors inducing cellular apoptosis; on the other hand, the N-terminal truncated isoforms (ΔNp73) can inhibit the transcripttional function of p53 and TAp73 [20].…”

Section: Introductionmentioning

confidence: 99%

Hypertension effects on p73 expression in the rat circumventricular organs and cerebrospinal fluid

Carmona-Calero¹,

González-Marrero²,

Castaneyra-Martin³

et al. 2012

WJNS

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ABSTRACTand SHR were used. The paraffin sections containing the CVO were immunohistochemically processed with anti-TAp73 and by western blot, p73 bands in the CSF and circumventricular organ extract were also identified. The western blot study showed bands marked with p73 in the CSF and CVO, the p73 band expression was bigger in the SHR than in the WKY rats. We also found stronger markings in the SFO, SCO and AP of the hypertensive rats than in the WKY rats. It could be concluded that hypertension in the SHR produces alterations in the relationship between the p73 protein, circumventricular structures and CSF.

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Developmental Roles of p73 in Cajal-Retzius Cells and Cortical Patterning

Cited by 120 publications

References 64 publications

Stromal-Derived Factor-1 (CXCL12) Regulates Laminar Position of Cajal-Retzius Cells in Normal and Dysplastic Brains

Stromal-Derived Factor-1 (CXCL12) Regulates Laminar Position of Cajal-Retzius Cells in Normal and Dysplastic Brains

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

Hypertension effects on p73 expression in the rat circumventricular organs and cerebrospinal fluid

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