Cerebellar GABAergic progenitors adopt an external granule cell-like phenotype in the absence of Ptf1a transcription factor expression.
We report in this study that, in the cerebellum, the pancreatic transcription factor Ptf1a is required for the specific generation of Purkinje cells (PCs) and interneurons. Moreover, granule cell progenitors in the external GCL (EGL) appear to be unaffected by deletion of Ptf1a. Cell lineage analysis in Ptf1a(Cre/Cre) mice was used to establish that, in the absence of Ptf1a expression, ventricular zone progenitors, normally fated to produce PCs and interneurons, aberrantly migrate to the EGL and express typical markers of these cells, such as Math1, Reelin, and Zic1/2. Furthermore, these cells have a fine structure typical of EGL progenitors, indicating that they adopt an EGL-like cell phenotype. These findings indicate that Ptf1a is necessary for the specification and normal production of PCs and cerebellar interneurons. Moreover, our results suggest that Ptf1a is also required for the suppression of the granule cell specification program in cerebellar ventricular zone precursors.
Pascual
Marta
M
Institut de Recerca Biomèdica, Parc Científic de Barcelona, Universitat de Barcelona, Josep Samitier 1-5, E-08028 Barcelona, Spain.
Abasolo
Ibane
I
Mingorance-Le Meur
Ana
A
Martínez
Albert
A
Del Rio
José A
JA
Wright
Christopher V E
CV
Real
Francisco X
FX
Soriano
Eduardo
E
D000818:Animals; D019070:Cell Lineage; D049109:Cell Proliferation; D002470:Cell Survival; D002552:Cerebral Ventricles / Q000166:cytology; D004622:Embryo, Mammalian / Q000166:cytology / Q000648:ultrastructure; D005260:Female; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D019426:Integrases / Q000378:metabolism; D007395:Interneurons / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D008954:Models, Biological; D010641:Phenotype; D011689:Purkinje Cells / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000091042:Reelin Protein; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D012333:RNA, Messenger; D000091042:Reelin Protein; D014157:Transcription Factors; C062602:transcription factor PTF1; D005680:gamma-Aminobutyric Acid; C045073:Cre recombinase; D019426:Integrases; C000717128:Reln protein, mouse