Neurotrophin receptor-mediated death of misspecified neurons generated from embryonic stem cells lacking Pax6.
Pax6-positive radial glial (RG) cells are the progenitors of most glutamatergic neurons in the cortex, a lineage that can be recapitulated in vitro using embryonic stem (ES) cells. We show here that ES cells lacking Pax6, a transcription factor long known to be essential for cortical development, generate Mash1-positive RG cells that differentiate in GABAergic neurons. These neurons express high levels of the neurotrophin receptor p75NTR causing their rapid death. Pax6 function was also investigated following transplantation of ES cells in the developing chick telencephalon and in mice lacking both Pax6 and p75NTR. Taken together, our results indicate that reliable predictions can be made with cultured ES cells when used to explore the role of genes impacting early aspects of mammalian neurogenesis. They also provide a novel opportunity to compare the molecular constituents of glutamatergic with those of GABA-ergic neurons and to explore the mechanisms of their generation.
Nikoletopoulou
Vassiliki
V
Biozentrum, University of Basel, 4056 Basel, Switzerland.
Plachta
Nicolas
N
Allen
Nicolas D
ND
Pinto
Luisa
L
Götz
Magdalena
M
Barde
Yves-Alain
YA
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D016923:Cell Death; D002454:Cell Differentiation; D002460:Cell Line; D019070:Cell Lineage; D002540:Cerebral Cortex / Q000196:embryology / Q000378:metabolism; D002642:Chick Embryo; D053595:Embryonic Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000637:transplantation; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D005865:Gestational Age; D018698:Glutamic Acid / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000637:transplantation; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000637:transplantation; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D017475:Receptors, Nerve Growth Factor / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D013687:Telencephalon / Q000196:embryology / Q000378:metabolism; D014162:Transfection; D014212:Tretinoin / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D005136:Eye Proteins; D018698:Glutamic Acid; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D017475:Receptors, Nerve Growth Factor; D012097:Repressor Proteins; D014212:Tretinoin; D005680:gamma-Aminobutyric Acid; C499317:Ascl1 protein, mouse; C000605732:Pax6 protein, mouse; C517634:Ngfr protein, mouse