Telencephalic neural precursor cells show transient competence to interpret the dopaminergic niche of the embryonic midbrain.
Neural Precursor Cells (NPCs) generate complex stereotypic arrays of neuronal subtypes in the brain. This process involves the integration of patterning cues that progressively restrict the fate of specific NPCs. Yet the capacity of NPCs to interpret foreign microenvironments during development remains poorly defined. The aim of this work was to test the competence of mouse telencephalic NPCs to respond to the dopaminergic niche of the mesencephalon. Telencephalic NPCs isolated from midgestation mouse embryos (E10.5) and transplanted to age-matched mesencephalic explants efficiently differentiated into neurons but were largely unable to produce midbrain dopaminergic (mDA) neurons. Instead, E10.5 telencephalic NPCs behaved as restricted gabaergic progenitors that maintained ectopic expression of Foxg1 and Pax6. In contrast, E8.5 telencephalic NPCs were able to differentiate into Lmx1a(+)/Foxa2(+)/TH(+) neurons in the dopaminergic niche of the mesencephalic explants. In addition, these early telencephalic NPCs showed region-dependent expression of Nkx6.1, Nkx2.2 and site-specific differentiation into gabaergic neurons within the mesencephalic tissue. Significant dopaminergic differentiation of E8.5 telencephalic NPCs was not observed after transplantation to E12.5 mesencephalic explants, suggesting that inductive signals in the dopaminergic niche rapidly decay after midgestation. Moreover, we employed transplantation of embryonic stem cells-derived precursors to demonstrate that extinction of inductive signals within the telencephalon lags behind the commitment of residing NPCs. Our data indicate that the plasticity to interpret multiple instructive niches is an early and ephemeral feature of the telencephalic neural lineage.
Department of Developmental Genetics and Molecular Physiology, Instituto de Biotecnología, Universidad Nacional Autónoma de México, AP 510-3, Cuernavaca, Mor. 62250, Mexico.
José-Manuel
JM
Baizabal
Concepción
C
Valencia
Gilda
G
Guerrero-Flores
Luis
L
Covarrubias
D000818:Animals; D019521:Body Patterning / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism*; D005136:Eye Proteins / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000378:metabolism; D051542:Hepatocyte Nuclear Factor 3-beta / Q000378:metabolism; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins / Q000378:metabolism; D060850:LIM-Homeodomain Proteins; D008636:Mesencephalon / Q000196:embryology*; D051379:Mice; D008856:Microscopy, Fluorescence; D009419:Nerve Tissue Proteins / Q000378:metabolism; D058953:Neural Stem Cells / Q000378:metabolism* / Q000637:transplantation; D055495:Neurogenesis; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D013687:Telencephalon / Q000166:cytology*; D014157:Transcription Factors
D005136:Eye Proteins; D051858:Forkhead Transcription Factors; C496503:Foxa2 protein, mouse; C489565:Foxg1 protein, mouse; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; C489692:Lmx1a protein, mouse; D009419:Nerve Tissue Proteins; C000715627:Nkx2-2 protein, mouse; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins; D014157:Transcription Factors; D051542:Hepatocyte Nuclear Factor 3-beta; D004298:Dopamine