Ptf1a, a bHLH transcriptional gene, defines GABAergic neuronal fates in cerebellum

Mikio Hoshino; Shoko Nakamura; Kiyoshi Mori; Takeshi Kawauchi; Mami Terao; Yoshiaki V Nishimura; Akihisa Fukuda; Toshimitsu Fuse; Naoki Matsuo; Masaki Sone; Masahiko Watanabe; Haruhiko Bito; Toshio Terashima; Christopher V E Wright; Yoshiya Kawaguchi; Kazuwa Nakao; Yo-Ichi Nabeshima

doi:10.1016/j.neuron.2005.06.007

Ptf1a, a bHLH transcriptional gene, defines GABAergic neuronal fates in cerebellum

Neuron. 2005 Jul 21;47(2):201-13. doi: 10.1016/j.neuron.2005.06.007.

Authors

Mikio Hoshino¹, Shoko Nakamura, Kiyoshi Mori, Takeshi Kawauchi, Mami Terao, Yoshiaki V Nishimura, Akihisa Fukuda, Toshimitsu Fuse, Naoki Matsuo, Masaki Sone, Masahiko Watanabe, Haruhiko Bito, Toshio Terashima, Christopher V E Wright, Yoshiya Kawaguchi, Kazuwa Nakao, Yo-Ichi Nabeshima

Affiliation

¹ Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan. mikio@lmls.med.kyoto-u.ac.jp

PMID: 16039563
DOI: 10.1016/j.neuron.2005.06.007

Abstract

The molecular machinery governing glutamatergic-GABAergic neuronal subtype specification is unclear. Here we describe a cerebellar mutant, cerebelless, which lacks the entire cerebellar cortex in adults. The primary defect of the mutant brains was a specific inhibition of GABAergic neuron production from the cerebellar ventricular zone (VZ), resulting in secondary and complete loss of external germinal layer, pontine, and olivary nuclei during development. We identified the responsible gene, Ptf1a, whose expression was lost in the cerebellar VZ but was maintained in the pancreas in cerebelless. Lineage tracing revealed that two types of neural precursors exist in the cerebellar VZ: Ptf1a-expressing and -nonexpressing precursors, which generate GABAergic and glutamatergic neurons, respectively. Introduction of Ptf1a into glutamatergic neuron precursors in the dorsal telencephalon generated GABAergic neurons with representative morphological and migratory features. Our results suggest that Ptf1a is involved in driving neural precursors to differentiate into GABAergic neurons in the cerebellum.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Age Factors
Animals
Animals, Newborn
Bromodeoxyuridine / metabolism
Calbindin 2
Calbindins
Cell Count / methods
Cell Death / physiology
Cell Differentiation / physiology
Cell Size
Cerebellum / abnormalities
Cerebellum / cytology*
Cerebellum / embryology
Cerebellum / metabolism*
Embryo, Mammalian
Gene Expression Regulation, Developmental / physiology
Glial Fibrillary Acidic Protein / metabolism
Green Fluorescent Proteins
Helix-Loop-Helix Motifs / physiology*
Immunohistochemistry / methods
In Situ Hybridization, Fluorescence / methods
In Situ Nick-End Labeling / methods
In Vitro Techniques
Mice
Mice, Mutant Strains
Models, Neurological
NIMA-Interacting Peptidylprolyl Isomerase
Neurons / classification
Neurons / physiology*
Peptidylprolyl Isomerase / physiology*
Phenotype
RNA, Messenger / biosynthesis
Reverse Transcriptase Polymerase Chain Reaction / methods
S100 Calcium Binding Protein G / metabolism
beta-Galactosidase / metabolism
gamma-Aminobutyric Acid / metabolism*

Substances

Calbindin 2
Calbindins
Glial Fibrillary Acidic Protein
NIMA-Interacting Peptidylprolyl Isomerase
RNA, Messenger
S100 Calcium Binding Protein G
Green Fluorescent Proteins
gamma-Aminobutyric Acid
beta-Galactosidase
Peptidylprolyl Isomerase
Pin1 protein, mouse
Bromodeoxyuridine