Abstract
p73 transcription factor belongs to one of the most important gene families in vertebrate biology, the p53-family. Trp73 gene, like the other family members, generates multiple isoforms named TA and DNp73, with different and, sometimes, antagonist functions. Although p73 shares many biological functions with p53, it also plays distinct roles during development. Trp73 null mice (p73KO from now on) show multiple phenotypes as gastrointestinal and cranial hemorrhages, rhinitis and severe central nervous system defects. Several groups, including ours, have revisited the apparently unrelated phenotypes observed in total p73KO and revealed a novel p73 function in the organization of ciliated epithelia in brain and trachea, but also an essential role as regulator of ependymal planar cell polarity. Unlike p73KO or TAp73KO mice, tumor-prone Trp53−/− mice (p53KO) do not present ependymal ciliary or planar cell polarity defects, indicating that regulation of ciliogenesis and PCP is a p73-specific function. Thus, loss of ciliary biogenesis and epithelial organization might be a common underlying cause of the diverse p73KO-phenotypes, highlighting Trp73 role as an architect of the epithelial tissue. In this review we would like to discuss the data regarding p73 role as regulator of ependymal cell ciliogenesis and PCP, supporting the view of the Trp73-mutant mice as a model that uncouples ciliogenesis from PCP and a possible model of human congenital hydrocephalus.
Highlights
The p53-family is constituted by the transcription factors p53, p63 and p73
TAp73 regulation of polarized microtubules dynamics is important for the asymmetric localization of Planar Cell Polarity (PCP)-core proteins at opposite sides of the apical membrane at MT anchoring points at cell junctions
These actin and microtubule networks allow the junctional localization of PCP-core protein complexes [Vangl2 and Frizzled] and the formation of signaling complexes at basal body (BB)-clusters and at the base of cilia axoneme [Dvl2, Rac1 and Fat4]. p73 deficiency results in severe defects in ciliogenesis and the loss of apical cytoskeleton dynamics in ependymal cells (ECs), which correlates with impaired BB docking, lack of asymmetric localization PCP-proteins and the disassembly of the signaling complexes associated with the cilia BB, resulting in lack of translational and rotational polarity in these cells and disorganization of cilia. (C) Representative scanning electron microscopy (SEM) images of WT and p73KO lateral ventricle wall (LW) whole-mounts (WMs) at P15
Summary
The p53-family is constituted by the transcription factors p53, p63 and p73. The tumor suppressive function of p53 largely resides in its capacity to sense potentially oncogenic and genotoxic stress conditions, and to coordinate a complex set of molecular events leading to growth restraining responses and, to senescence and/or apoptosis. TAp73 regulation of polarized microtubules dynamics is important for the asymmetric localization of PCP-core proteins at opposite sides of the apical membrane at MT anchoring points at cell junctions.
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