Figure 4.

Comparative analysis of supragranular-enriched genes from the cortex of humans and mice in adulthood (A) and in development (B-D). In adulthood, the expression of some supragranular-enriched genes such as NEFH, SYT2, VAMP1, and CRYM are expressed in layers III in humans but are less so in mice. The expression of NEFH in the cortex is protracted in humans relative to mice once variation in developmental schedules are controlled for. This is evident from comparative analyses of (A) NEFH expression from in situ hybridization in the cortex of humans and in mice, (B) RNA sequencing data from the frontal cortex of humans and in mice, as well as (C) and from quantitative investigations of NEFH expression across layers of the cortex in humans and in mice. (A) NEFH expression increases shortly after birth in mice but remains relatively poorly expressed at roughly comparable ages in humans. (B) NEFH expression from an RNA sequencing data from the frontal cortex of humans and mice increase with age in both species but they appear to increase for longer in humans than in mice once variation in developmental schedules are controlled for. (C) Quantitative investigations of NEFH expression intensity between layers II-IV versus V-VI in the cortex of humans and in mice show that the relative expression of NEFH increases for longer in humans than in mice once variation in developmental schedules are controlled for, which suggests that the development of NEFH expression in superficial layers is protracted in humans relative to mice. These findings demonstrate that the protracted time course of NEFH expression from bulk samples in humans relative to mice may be accounted for by the protracted expression of NEFH expression in supragranular layers in humans. These graphs are modified from 14 and 17.