Pluto Bioinformatics

GSE119362: Neonatal Tbr1 Dosage Controls Cortical Layer 6 Connectivity.

Bulk RNA sequencing

An understanding of how heterozygous loss-of-function mutations in ASD risk genes, such as TBR1, contribute to ASD remains elusive.; Conditional Tbr1 deletion during late mouse gestation in cortical layer 6 neurons (Tbr1layer6 mutants) provides novel insights into its function, including dendritic patterning, synaptogenesis, and cell intrinsic physiology.; These phenotypes occur in heterozygotes, providing insights into mechanisms that may underlie ASD pathophysiology. Restoring expression of Wnt7b, largely rescues the synaptic deficit in Tbr1layer6 mutant neurons.; Furthermore, Tbr1layer6 heterozygotes have increased anxiety-like behavior, a phenotype seen ASD. Integrating TBR1 ChIP-Seq and RNA-Seq data from layer 6 neurons, and activity of TBR1 bound candidate enhancers, provides evidence for how TBR1 regulates layer 6 properties.; Moreover, several putative TBR1 targets are ASD risk genes, placing TBR1 in a central position both for ASD risk and for regulating transcriptional circuits that control multiple steps in layer 6 development essential for the assembly of neural circuits. SOURCE: Siavash Fazel Darbandi (siavash.fazeldarbandi@ucsf.edu) - State/Rubenstein University of California San Francisco