P2.37. COMPARATIVE HISTOLOGICAL ANALYSIS OF CORTICAL DEVELOPMENT IN BTBR AND C57BL/6 MOUSE MODELS AT MID-GESTATION STAGES: IMPLICATIONS FOR NEURODEVELOPMENTAL DISORDERS
Joanna Czyrska, Silvestre Sampino, Maria Pia Viscomi, Marta Ziętek, Małgorzata Cybulska
Institute of Genetics and Animal Biotechnology of Polish Academy of Sciences
INTRODUCTION: Disruptions in mid-gestational cortical development have been implicated in the etiology of autism spectrum disorder (ASD). The BTBR T+ Itpr3tf/J (BTBR) mouse strain, a widely used ASD model, exhibits behavioral and anatomical abnormalities resembling the human condition, whereas the C57BL/6 (B6) strain serves as a comparison for typical development.
AIM(S): In this study, we investigated early developmental differences between BTBR and B6 fetuses at 12.5 and 15.5 days post coitum (dpc).
METHOD(S): Body weight measurements and somite counts were used to assess systemic growth and developmental staging.
Histological analysis with hematoxylin and eosin staining was performed to evaluate cortical architecture at 12.5 and 15.5 dpc.
Transcriptomic profiling was conducted on fetal heads and placentas to identify strain-specific gene expression patterns.
RESULTS: BTBR fetuses exhibited consistently lower body weights across pregnancy, indicating systemic growth restriction.
Somite counts at 12.5 dpc showed no significant differences, confirming equivalent developmental staging.
Histology revealed no differences in cortical thickness at 12.5 dpc. By 15.5 dpc, BTBR cortices displayed a thinner ventricular zone and a thicker intermediate zone compared to B6 controls, suggesting altered neurogenesis and/or neuroprogenitor migration.
Transcriptomic profiling showed significant gene expression differences between strains, with greater divergence in placental tissue than fetal tissue.
CONCLUSIONS: BTBR fetuses exhibit early structural and transcriptional alterations during cortical development. The pronounced gene expression differences in the placenta suggest a potential non-neural contributor to neurodevelopmental outcomes. Current efforts to generate BTBR-B6 chimeric mice aim to dissect cell-autonomous versus non-cell-autonomous contributions to neurodevelopment. These findings underscore the importance of early development in shaping long-term neurodevelopmental trajectories.
FINANCIAL SUPPORT: This research was supported by the National Science Center, Poland (grant no. 2020/39/B/NZ4/02105).