Growth defects in the dorsal pallium after genetically targeted ablation of principal preplate neurons and neuroblasts: a morphometric analysis.

TitleGrowth defects in the dorsal pallium after genetically targeted ablation of principal preplate neurons and neuroblasts: a morphometric analysis.
Publication TypeJournal Article
Year of Publication2010
AuthorsFisher, R, Xie Y-Y
JournalASN neuro
Volume2
Issue5
Paginatione00046
Date Published2010
ISSN1759-0914
KeywordsAnimals, Animals, Newborn, Cross-Sectional Studies, Female, Gene Silencing, Gene Targeting, Mice, Mice, Transgenic, Neural Stem Cells, Neurons, Pregnancy, Random Allocation, Telencephalon
Abstract

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.

DOI10.1042/AN20110027
Alternate JournalASN Neuro