Fig. 3.

p73 regulates ependymal cell development, ciliogenesis and planar cell polarity. (A) Wild-type (WT) ependymal cells (ECs) form perinatally from GFAP-positive radial glial cells, which transform into a central stem cell (B-cell, remaining GFAP-positive) and surrounding, multi- and bi-ciliated ECs (becoming GFAP-negative). Together they form neuro-regenerative units along the ventricular walls, called pinwheels. p73-deficient ECs fail to organize into pinwheels, thereby disrupting subventricular zone niche architecture and function, and exhibiting defective ciliogenesis with disturbed cerebrospinal fluid (CSF) flow. Wild-type cells have cilia asymmetrically distributed at the anterior apical surface, and all cilia are polarized with the same orientation. p73KO cells have lost their polarization, with basal bodies distributed throughout the apical surface. (B) Other as-yet-undescribed direct TAp73 targets in ciliogenesis might also play a role in this process (indicated by the question mark). p73 is also essential for the polarized junctional assembly of PCP core proteins and the asymmetric localization of their downstream signaling effectors. Mechanistically, TAp73 regulates translational PCP (asymmetrical polarization of cilia clusters at the anterior apical surface) and actin dynamics through the direct transcriptional induction of myosin light-chain kinase (Mlck), which modulates non-muscle myosin-II (NM-II) activity, thereby affecting actin and microtubular transport dynamics, as well as Golgi organization.