The BrainSpan Atlas of the Developing Human Brain (Allen Institute) is a key resource for investigating transcriptional programs that shape human brain development. A central element is a set of high-quality, web-based neuroanatomical reference atlases that allow gene-expression data to be compared directly with expertly annotated anatomy, including integrated in situ hybridization (ISH) information. In the BrainSpan pipeline, a 21 post-conception week human brainstem (GW21) was mapped using 41 Nissl-stained sections. Dr. Sengul created a prenatal digital brainstem reference atlas by defining detailed labels and anatomical boundaries. ISH profiling relied on a curated gene panel (not genome-wide assays), prioritizing canonical markers, genes linked to neocortical development and disease, and genes overlapping the Allen Developing Mouse Brain Atlas. Notable enrichments included CALB2 (calretinin) in the solitary nucleus, dorsal paramedian nucleus, and cochlear nucleus; GRIK2 in medullary reticular nuclei and the gracile/cuneate nuclei; NPY in the dorsal motor nucleus of the vagus and intermediate reticular nucleus; and SST in the locus coeruleus, spinal trigeminal nucleus (oral part), vestibular nuclei, and red nucleus. Additional regionally enriched markers included ERBB4 in substantia nigra; NTRK2 (TrkB) in the mesencephalic trigeminal nucleus, inferior olive, hypoglossal/vestibular nuclei, dorsal motor nucleus of the vagus, and dorsal raphe; ZIC1 in cochlear nuclei; SATB2 in parabrachial nuclei; PLXNA2 in the corticospinal tract; MECP2 in substantia nigra; and GAP43 in the inferior colliculus. Overall, the GW21 brainstem atlas provides a mid-gestation baseline for interpreting molecular programs underlying brainstem function and disease-relevant pathways, supporting translational studies of later neurological and neuropsychiatric vulnerability.
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