title: Rp58 is essential for the growth and patterning of the cerebellum and for glutamatergic and GABAergic neuron development.
abstract: Cerebellum development depends on the correct differentiation of progenitors into neurons, a process controlled by a transcriptional program that remains poorly understood. Here we show that neural-specific deletion of the BTB/POZ zinc-finger transcription factor-encoding gene Rp58 (Znf238, Zfp238) causes severe cerebellar hypoplasia and developmental failure of Purkinje neurons, Bergmann glia and granule neurons. Deletion of Rp58 in mouse embryonic Atoh1(+) progenitors leads to strong defects in growth and foliation owing to its crucial role in the differentiation of granule neurons. Analysis of the Rp58 mutant at E14.5 demonstrates that Rp58 is required for the development of both glutamatergic and GABAergic neurons. Rp58 mutants show decreased proliferation of glutamatergic progenitors at E14.5. In addition, Rp58 ablation results in a reduced number of GABAergic Pax2(+) neurons at E16.5 together with defects in the transcriptional program of ventricular zone progenitors. Our results indicate that Rp58 is essential for the growth and organization of the cerebellum and regulates the development of both GABAergic and glutamatergic neurons.
authors.affiliation: The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA.
authors.forename: Valérie
authors.initials: V
authors.lastname: Baubet
authors.forename: Chaomei
authors.initials: C
authors.lastname: Xiang
authors.forename: Aliah
authors.initials: A
authors.lastname: Molczan
authors.forename: Laura
authors.initials: L
authors.lastname: Roccograndi
authors.forename: Svetlana
authors.initials: S
authors.lastname: Melamed
authors.forename: Nadia
authors.initials: N
authors.lastname: Dahmane
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D019521:Body Patterning / Q000502:physiology*; D002531:Cerebellum / Q000196:embryology* / Q000254:growth & development; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D055495:Neurogenesis / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction; D012097:Repressor Proteins / Q000378:metabolism / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D012097:Repressor Proteins; C500943:Atoh1 protein, mouse; C520669:Zbtb18 protein, mouse