Extended Data Fig. 4: Expression of RA-synthesizing enzymes in the developing human and macaque cortex.
From: Regulation of prefrontal patterning and connectivity by retinoic acid
a, Spatiotemporal expression of genes encoding RA synthesizing enzymes, ALDH1A1, 2 and 3, in eleven neocortical areas of human and macaque during prenatal and postnatal development using BrainSpan (brainspan.org) and PsychENCODE (evolution.psychencode.org) RNA-seq data17,19. Red and blue lines indicate human and macaque, respectively, and dotted lines represent the non-PFC expression in the PFC plot. Vertical grey box demarcates mid-fetal developmental periods. Predicted ages, timeline of human and macaque development, and the associated periods are shown below19,63. b, Heat map of normalized (z-score) microarray signals computed for genes encoding RA synthesizing enzymes from the BrainSpan human prenatal laser microdissection microarray data63 (brainspan.org). Left columns represent gene name and specific probe. Each column represents regions of the brain labelled above the heat maps. Darker reds represent high expression levels. c, Anteroposterior visual representation of human ALDH1A1 and ALDH1A3 expression at PCW 16 and 15 respectively from BrainSpan atlas58. ALDH1A1, 2 and 3 expression in mid-fetal human (PCW 19, 19, 20) (d, left) and macaque (PCD 80, 80, 110) (e, left) meninges. Immunostaining for ALDH1A1 and TH in human PCW 12 and 22 brains (d, right), and in macaque PCD 76 brain (e, right). White arrowheads, and open arrowheads indicate ALDH1A1+;TH+ and ALDH1A1+;TH- axons in the subplate, respectively. NCX, neocortex; PU, putamen; NAC, nucleus accumbens; CA, CA subfields of hippocampus. Errors bars: S.D. N = 3. f, Anterior to posterior expression of ALDH1A3 mRNA in human (PCW 21), macaque (PCD 140) and mouse (PD 0) brain. N = 2 for human and macaque, N = 3 for mouse. g, Western blot using ALDH1A3 antibody in human (PCW 20), macaque (PCD 114) and mouse (PD 0) frontal cortex areas. In macaque and human, there are two bands that are likely to represent ALDH1A3 (56 kDa) and ALDH1A1 (54 kDa). Experiments were repeated at least two times for each animal species. See Extended Data Fig. 6a for schemas of frontal areas.
