Growth defects in the dorsal pallium after genetically targeted ablation of principal preplate neurons and neuroblasts: a morphometric analysis.
ASN Neuro
; 2(5): e00046, 2010 Oct 04.
Article
en En
| MEDLINE
| ID: mdl-20957077
The present study delineates the large-scale, organic responses of growth in the dorsal pallium to targeted genetic ablations of the principal PP (preplate) neurons of the neocortex. Ganciclovir treatment during prenatal development [from E11 (embryonic age 11) to E13] of mice selectively killed cells with shared S-phase vulnerability and targeted expression of a GPT [golli promoter transgene; GPT linked to HSV-TK (herpes simplex virus-thymidine kinase), τ-eGFP and lacZ reporters] localized in PP neurons and their intermediate progenitor neuroblasts. The volume, area and thickness of the pallium were measured in an E12-P4 (postnatal age 4) longitudinal study with comparisons between ablated (HSV-TK(+/0)) and control (HSV-TK(0/0)) littermates. The extent of ablations was also systematically varied, and the effect on physical growth was assessed in an E18 cross-sectional study. The morphological evidence obtained in the present study supports the conclusion that genetically targeted ablations delay the settlement of the principal PP neurons of the dorsal pallium. This leads to progressive and substantial reductions of growth, despite compensatory responses that rapidly replace the ablated cells. These growth defects originate from inductive cellular interactions in the proliferative matrix of the ventricular zone of the pallium, but are amplified by subsequent morphogenic and trophic cellular interactions. The defects persist during the course of prenatal and postnatal development to demonstrate a constrained dose-response relationship with the extent of specific killing of GPT neurons. The defects propagate simultaneously in both the horizontal and vertical cytoarchitectural dimensions of the developing pallium, an outcome that produces a localized shortfall of volume in the telencephalic vesicles.
Palabras clave
BrdU, bromodeoxyuridine; CP/D, cortical plate/distal division; CP/P, cortical plate/proximal division; E11, embryonic age 11; GPT, golli promoter transgene; HSV-TK, herpes simplex virus-thymidine kinase; IZ, intermediate zone; MBP, myelin basic protein; NA, numerical aperture; P4, postnatal age 4; PP, preplate; Pα, probability of type I error; SP, subplate; SVZ, subventricular zone; TUNEL, terminal deoxynucleotidyltransferase-mediated dUTP nick-end labelling; VZ, ventricular zone; VZ/SVZ, the combined VZ and SVZ; X-gal, 5-bromo-4-chloro-3-indolyl-ß-d-galactoside; df, degrees of freedom; forebrain growth; morphogenesis; neocortex; pathogenesis; preplate; targeted ablation
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Telencéfalo
/
Marcación de Gen
/
Silenciador del Gen
/
Células-Madre Neurales
/
Neuronas
Tipo de estudio:
Observational_studies
/
Prevalence_studies
/
Risk_factors_studies
Límite:
Animals
/
Pregnancy
Idioma:
En
Revista:
ASN Neuro
Asunto de la revista:
NEUROLOGIA
/
QUIMICA
Año:
2010
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos