p73 is required for ependymal cell maturation and neurogenic SVZ cytoarchitecture

Abstract

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

Tissue-specific roles of p73 in development and homeostasis

“…3). Thus, p73 is required for ependymal maturation and neurogenic SVZ cytoarchitecture (Fujitani et al, 2017;Gonzalez-Cano et al, 2016). TAp73KO ECs exhibit the same PCP and basalbody anchoring defects, identifying TAp73 as the regulator of PCP (Fuertes-Alvarez et al, 2018).…”

“…In addition to the defects described above, p73KO mice also exhibit striking airway infections, female and male infertility, and runting. TAp73 was found to function as a master transcriptional regulator governing motile multiciliogenesis, as the common unifying mechanism underlying these disparate p73KO phenotypes (Fujitani et al, 2017;Gonzalez-Cano et al, 2016;Marshall et al, 2016;Nemajerova et al, 2016).…”

GemC1 is a critical switch for neural stem cell generation in the postnatal brain

“…Mouse brains were analyzed at P7, and Cre recombination was monitored by GFP expression. To examine whether the ependymal cell population is affected, we performed immunofluorescence experiments using anti‐p73 antibody, a transcription factor that was highlighted for its critical role in ependymal cell generation (Fujitani et al, ; Gonzalez‐Cano et al, ), acting upstream of Foxj1 (Marshall et al, ; Nemajerova et al, ). In the control mouse brains, 30% of GFP+ cells were co‐expressing p73, whereas p73+ cells were rarely detected in GemC1 Fl/Fl electroporated brains, representing only 1.7% of GFP+ cells (Supporting Information Figure S2B, C).…”

Organized Neurogenic-Niche-Like Pinwheel Structures Discovered in Spinal Cord Tissue-Derived Neurospheres

“…The neurogenic capacity of the mouse SVZ depends on the capability of ependymal cells to assemble into pinwheels; unique structures that constitute real regenerative units (Paez-Gonzalez et al, 2011;Gonzalez-Cano et al, 2016). In neurogenic regions of the SVZ in the mouse adult brain, the cytoarchitecture of the pinwheel unit constitutes a core of ciliated astrocytes surrounded by ciliated ependymal cells (Mirzadeh et al, 2008).…”