Open AccessZfp423 controls proliferation and differentiation of neural precursors in cerebellar vermis formation
Author(s) -
Wendy Alcaraz,
David Gold,
Éric Raponi,
Peter M. Gent,
Dorothy Concepcion,
Bruce A. Hamilton
Publication year - 2006
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0609184103
Subject(s) - cerebellum , neurogenesis , neuroscience , neural development , biology , cerebellar vermis , neural stem cell , hippocampal formation , corpus callosum , progenitor , cellular differentiation , transcription factor , progenitor cell , granule cell , microbiology and biotechnology , anatomy , stem cell , dentate gyrus , genetics , gene
Neural stem cells and progenitors in the developing brain must choose between proliferation with renewal and differentiation. Defects in navigating this choice can result in malformations or cancers, but the genetic mechanisms that shape this choice are not fully understood. We show by positional cloning that the 30-zinc finger transcription factor Zfp423 (OAZ) is required for patterning the development of neuronal and glial precursors in the developing brain, particularly in midline structures. Mutation ofZfp423 results in loss of the corpus callosum, reduction of hippocampus, and a malformation of the cerebellum reminiscent of human Dandy–Walker patients. Within the cerebellum,Zfp423 is expressed in both ventricular and external germinal zones. Loss ofZfp423 results in diminished proliferation by granule cell precursors in the external germinal layer, especially near the midline, and abnormal differentiation and migration of ventricular zone-derived neurons and Bergmann glia.