Dynamic expression of the p53 family members p63 and p73 in the mouse and human telencephalon during development and in adulthood

Hernández-Acosta, N. Carolina; Cabrera-Socorro, Alfredo; Morlans, Mercedes Pueyo; Delgado, Francisco J. González; Suárez-Solá, M. Luisa; Sottocornola, Roberta; Lü, Xin; González‐Gómez, Miriam; Meyer, Gundela

doi:10.1016/j.brainres.2010.11.041

Cited by 28 publications

(35 citation statements)

References 74 publications

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“…Thus, we conclude that p63 plays no apparent role in the development of the central nervous system. This finding is in complete agreement with an independent concomitant recent report from the Meyer lab 7 but not with the idea that p63 is required for survival of neural precursors in the brain.…”

Section: Introductionsupporting

confidence: 89%

“…Global p63 -/-mice, which express normal levels of p73, were found to lack any brain malformations and exhibit normal numbers of Cajal-Retzius cells. 7 maturation of neural stem cells into the three different lineages of neurons, astrocytes and oligodendrocytes. To this end, we used specific differentiation markers.…”

Section: Discussionmentioning

confidence: 99%

“…5 They are characterized by progressive cortical hypoplasia with ensuing ex vacuo hydrocephalus, present already in one third of animals at birth, 6 hippocampal dysgenesis with loss or truncation of the lower blade of the neurogenic dentate gyrus, 6 thinning of the neurogenic subventricular zone in the forbrain and loss of the Cajal-Retzius neurons. 7 Importantly, as recently established, this defect is largely due to p73's role as an essential the ancient p53 paralogs p63 and p73 regulate specific tissue formation, cell survival and cell death via their tA and ΔN isoforms. targeted disruption of the p73 locus leads to severe defects in the development of the central nervous system (CNS), and p73 has recently been shown to be an essential regulator of neural stem cell maintenance and differentiation in both embryonal and adult neurogenesis.…”

Section: Introductionmentioning

confidence: 99%

“…Thus, in developing sympathetic neurons an essential pro-apoptotic role was ascribed to the transactivating TAp63γ isoform, 14 perhaps balancing the anti-apoptotic pro-survival function of N-terminally truncated ΔNp63 and/or ΔNp73 isoforms, which are coexpressed in mature neurons. 2,7,12,14 From these findings it was proposed that p63 is a general and essential developmental regulator of all neuronal cells, particularly in the CNS. [15][16][17][18] In support of this notion, a recent experimental study describes an essential anti-apoptotic pro-survival function of ΔNp63 in neural precursor cells in the developing CNS of mouse embryos.…”

mentioning

confidence: 99%

“…Indeed, these results were challenged by the observation from us and others that the brain of p63 -/-mice did not display gross anatomical malformations at birth. 7 These disparate results raise the need to reassess the precise role of p63 in neural cell fate in a clean in vivo system that is not experimentally manipulated, i.e., in p63 -/-mice. Here we analyze in detail whether the ablation of all isoforms of p63 affects CNS development.…”

mentioning

confidence: 99%

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While p73 is essential, p63 is completely dispensable for the development of the central nervous system

Holembowski¹,

Schulz²,

Talos³

et al. 2011

Cell Cycle

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Section: Introductionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

While p73 is essential, p63 is completely dispensable for the development of the central nervous system

Holembowski¹,

Schulz²,

Talos³

et al. 2011

Cell Cycle

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Cortical hypoplasia and ventriculomegaly of p73‐deficient mice: Developmental and adult analysis

Medina-Bolívar

González‐Arnay

Talos

et al. 2014

J of Comparative Neurology

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Trp73, a member of the p53 gene family, plays a crucial role in neural development. We describe two main phenotypic variants of p73 deficiency in the brain, a severe one characterized by massive apoptosis in the cortex leading to early postnatal death and a milder, non-/low-apoptosis one in which 50% of pups may reach adulthood using an intensive-care breeding protocol. Both variants display the core triad of p73 deficiency: cortical hypoplasia, hippocampal malformations, and ventriculomegaly. We studied the development of the neocortex in p73 KO mice from early embryonic life into advanced age (25 months). Already at E14.5, the incipient cortical plate of the p73 KO brains showed a reduced width. Examination of adult neocortex revealed a generalized, nonprogressive reduction by 10-20%. Area-specific architectonic landmarks and lamination were preserved in all cortical areas. The surviving adult animals had moderate ventricular distension, whereas pups of the early lethal phenotypic variant showed severe ventriculomegaly. Ependymal cells of wild-type ventricles strongly express p73 and are particularly vulnerable to p73 deficiency. Ependymal denudation by apoptosis and reduction of ependymal cilia were already evident in young mice, with complete absence of cilia in older animals. Loss of p73 function in the ependyma may thus be one determining factor for chronic hydrocephalus, which leads to atrophy of subcortical structures (striatum, septum, amygdala). p73 Is thus involved in a variety of CNS activities ranging from embryonic regulation of brain size to the control of cerebrospinal fluid homeostasis in the adult brain via maintenance of the ependyma.

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p73 is required for ependymal cell maturation and neurogenic SVZ cytoarchitecture

Gonzalez-Cano

Fuertes-Alvarez

Robledinos-Antón

et al. 2015

Developmental Neurobiology

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The adult subventricular zone (SVZ) is a highly organized microenvironment established during the first postnatal days when radial glia cells begin to transform into type B‐cells and ependymal cells, all of which will form regenerative units, pinwheels, along the lateral wall of the lateral ventricle. Here, we identify p73, a p53 homologue, as a critical factor controlling both cell‐type specification and structural organization of the developing mouse SVZ. We describe that p73 deficiency halts the transition of the radial glia into ependymal cells, leading to the emergence of immature cells with abnormal identities in the ventricle and resulting in loss of the ventricular integrity. p73‐deficient ependymal cells have noticeably impaired ciliogenesis and they fail to organize into pinwheels, disrupting SVZ niche structure and function. Therefore, p73 is essential for appropriate ependymal cell maturation and the establishment of the neurogenic niche architecture. Accordingly, lack of p73 results in impaired neurogenesis. Moreover, p73 is required for translational planar cell polarity establishment, since p73 deficiency results in profound defects in cilia organization in individual cells and in intercellular patch orientation. Thus, our data reveal a completely new function of p73, independent of p53, in the neurogenic architecture of the SVZ of rodent brain and in the establishment of ependymal planar cell polarity with important implications in neurogenesis. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 730–747, 2016

show abstract

Dynamic expression of the p53 family members p63 and p73 in the mouse and human telencephalon during development and in adulthood

Cited by 28 publications

References 74 publications

While p73 is essential, p63 is completely dispensable for the development of the central nervous system

While p73 is essential, p63 is completely dispensable for the development of the central nervous system

Cortical hypoplasia and ventriculomegaly of p73‐deficient mice: Developmental and adult analysis

p73 is required for ependymal cell maturation and neurogenic SVZ cytoarchitecture

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