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

J Comp Neurol. 2014 Aug 1;522(11):2663-79. doi: 10.1002/cne.23556. Epub 2014 Apr 3.


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.

Keywords: apoptosis; cerebral cortex; cerebrospinal fluid; cilia; ependyma; lateral ventricles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Cell Count
  • Choroid Plexus / abnormalities
  • Choroid Plexus / growth & development
  • Choroid Plexus / physiopathology
  • DNA-Binding Proteins / deficiency*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Ependyma / abnormalities
  • Ependyma / growth & development
  • Ependyma / physiopathology
  • Fluorescent Antibody Technique
  • Hippocampus / abnormalities
  • Hippocampus / growth & development
  • Hippocampus / physiopathology
  • Hydrocephalus / pathology
  • Hydrocephalus / physiopathology*
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Mice, 129 Strain
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microscopy, Confocal
  • Neocortex / abnormalities*
  • Neocortex / growth & development*
  • Neocortex / physiopathology
  • Nuclear Proteins / deficiency*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / physiology*
  • Phenotype
  • Tumor Protein p73
  • Tumor Suppressor Proteins / deficiency*
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / physiology*


  • DNA-Binding Proteins
  • Nuclear Proteins
  • Trp73 protein, mouse
  • Tumor Protein p73
  • Tumor Suppressor Proteins