For each sample, selleck chemicals serial sections (20 μm) were collected from the cortex through to the cervical spinal cord. Every fifth section was costained with PKCγ (which marks the corticospinal tract), as well as NeuN and Hoescht to assist with matching levels between samples. Matched images corresponding to two regions were selected for analysis: (1) caudal to the basilar pons and (2) caudal to the pyramidal decussation. Images were analyzed in Metamorph. A constant threshold was applied to all images and the dorsal funiculus was masked. We then computed the area above threshold, which was normalized to the

area observed in wild-type mice. All measurements were conducted blind to genotype. Phylogenetic trees of murine Bhlhb5- and Prdm8-related proteins were created using the amino acid sequences of each murine protein and the ClustalW algorithm, with MyoD and G9A as the outgroups,

respectively. Apart from Zfp488, which we added based on our discovery of high similarity in protein sequences between Prdm8 and Zfp488 (E-value 3e-28), the decision of which family members to include in the phylogenetic analysis was based on previous analyses for bHLH (Ledent et al., 2002, Ledent and Vervoort, 2001 and Stevens et al., 2008) and Prdm families (Fumasoni et al., 2007). We thank M. Takeichi for supplying the Cdh11 mutant mice; A. Cano for supplying the HA-tagged E2-2B expression vector; SAR405838 E.C. Griffith for critical readings of the manuscript; D. Harmin for help with statistical analysis; P. Zhang for assistance with mouse colony management; the Intellectual and Developmental Disabilities Research Center (IDDRC) Gene Manipulation Core (M. Thompson, first Y. Zhou, and H. Ye); the Harvard Medical School Rodent Histopathology Core (R.T. Bronson), and the IDDRC Molecular Genetics Core. This work was supported by a Jane Coffin Childs Fellowship and a

Dystonia Medical Research Foundation Fellowship to S.E.R., NIH grant NS028829 to M.E.G., and the Developmental Disabilities Mental Retardation Research Center grant NIH-P30-HD-18655. “
“Adenosine-to-inosine (A-to-I) RNA editing is a versatile posttranscriptional mechanism that allows pinpoint recoding of transcripts at the resolution of single nucleotides. This mechanism can drastically impact both the expression levels and functional properties of resulting proteins, thereby expanding the repertoire of protein customization (Keegan et al., 2001). The underlying chemistry involves ADAR enzymes (adenosine deaminases acting on RNA) that catalyze the deamination of adenosine (A) to generate inosine (I) at certain nucleotide positions within RNA. Because inosine is decoded as guanosine (G) during translation, resulting protein products feature exquisitely customized amino acid composition.