Why Fish Anchor the Atlas
Cartilaginous and ray-finned fishes are the basal jawed vertebrates, and their brains mark the origin of the cellular architecture that all jawed brains build on. The BrainStorm sampling begins at the ~450-million-year-old shark lineage, and genomic studies of the water-to-land transition highlight lungfish and non-teleost ray-finned fishes as pivotal lineages. Because much of the analysis layer is restricted to orthologs retained across all species, fishes are where the deepest time-points of conserved cell-type identity are measured.
Root of the Jawed Brain
Our sampling starts from the most basal jawed vertebrates, cartilaginous fishes at about 450 million years before the present, and extends through the teleost radiation. Fish are the reference point against which ~450 million years of tetrapod divergence is measured.
Non-Teleost Bridges
Newly sequenced lungfish, bichir, reedfish and alligator gar provide cell-type resolution for lineages long flagged as pivotal in genomic studies of the water-to-land transition.
205,000 Fish Cells
Fish contribute 205,000 cells to the 492,121-cell analysis layer, the largest single lineage block and the deepest phylostratigraphic reference for cell-type age analyses.
About 450 Million Years, Conserved
The white-spotted bamboo shark (Chiloscyllium plagiosum) diverged from humans roughly 450 million years ago, yet ultra-conserved molecular signatures persist in its brain. Direct program-level comparison of the shark and humans exposes the deepest layer of jawed-vertebrate cell-type identity.
White-Spotted Bamboo Shark
Chiloscyllium plagiosum was newly sequenced across three libraries in this atlas, providing an early-diverging jawed-vertebrate anchor. Its conservation signal rests on direct comparison with humans across several core cell types.
CD74 · DOCK2 · VSIR
Shark microglia robustly express CD74 (microglial identity marker), DOCK2 (an innate immunity regulator in Alzheimer's disease) and VSIR (VISTA; a neuroinflammatory checkpoint), signaling deep conservation of the neuroimmune program.
MBP · NFASC
Shark oligodendrocytes up-regulate MBP (myelin structural protein) and NFASC (myelin targeting regulator) along with FRMD4A and PLEKHA8, echoing the myelination program of later-diverging lineages.
Paralog Switches and Ancient Excitatory Modules
Two insights on excitatory identity emerge from the fish lineages. First, the fish-to-tetrapod transition is marked by paralog-level diversification of the vesicular glutamate transporters. Second, ZIC5-driven excitatory programs appear far earlier than the mammalian neocortex.
SLC17A Paralog Transition
SLC17A6 and SLC17A7, the two vesicular glutamate transporter genes that define excitatory identity, show segregated usage across excitatory subtypes between teleost fishes and tetrapods, pointing to paralog-level diversification of excitatory programs at the fish-to-tetrapod transition.
ZIC5 Excitatory Modules
Multiple ZIC5-expressing excitatory subtypes are enriched across fishes, amphibians, reptiles and birds, indicating that ZIC-driven programs are an ancient excitatory neuron module involved in early pallial patterning, predating the mammalian neocortex.
Ancestral vs Derived Modules
Differential retention and amplification of these ZIC5 subtypes across lineages suggest the gradual specialization of cortical- or pallium-like circuits, with fish lineages preserving the ancestral-most configuration.
A Teleost P0-Dominant Myelin
A complete oligodendrocyte lineage with a basic myelin program is already assembled in early jawed vertebrates. Fishes stand apart in which myelin protein dominates: teleosts favor the P0 (MPZ) transcript, while tetrapods shift almost entirely to PLP1.
MPZ/(MPZ + PLP1)
The MPZ usage share is markedly higher in teleost fishes, median 0.561, than in tetrapods, median 0.003, a difference significant at two-sided Mann-Whitney p = 6.2e-14.
78 of 100 Species
The comparison entered 78 of the 100 analysis-layer species, the remainder lacking at least 50 oligodendrocyte-high cells to score the myelin module.
A Teleost Signature
The MPZ/P0-dominant usage profile is characteristic of the teleost fishes sampled here, and no confirmed MPZ/P0 ortholog could be identified in the white-spotted bamboo shark of our sampling.
Ancestral States Rule the Fish Brain
Fishes carry the ancestral microglial layer in force. Ancestral microglial clusters are enriched in basal lineages such as fishes and amphibians, while derived states such as Mic_011 dominate mammalian populations. In the fish brain, ancestral states dominate the microglial population.
Mic_005
The ancestral state Mic_005 is enriched in fishes, with a species-level median of 86% of microglia, at FDR = 3.8e-14.
Before the Tetrapod Transition
Ancestral clusters retain conserved pathways linked to hypoxia tolerance (HIF3A), redox homeostasis (SOD2) and phagocytic pruning (C1QA), with homologous states identified in cartilaginous fishes, suggesting origins that predate the vertebrate terrestrial transition.
Derived States Emerge
Whereas fishes are dominated by ancestral microglia, mammals show a tentative but consistent shift toward derived states such as Mic_011, enriched in mammals at FDR = 1.6e-12.
Non-Teleost Lineages, From Genomes to Cells
Four newly sequenced non-teleost fishes add cell-type resolution to lineages that genomic studies identify as pivotal for the water-to-land transition. Their placement outside the giant teleost radiation makes them especially informative for rooting conserved brain programs.
Protopterus annectens · West African Lungfish
Sequenced across three libraries in this atlas, the lungfish sits on the branch that leads toward tetrapods, bridging fish and land-vertebrate brain programs.
Polypterus senegalus · Gray Bichir
An early-branching ray-finned fish with lobed fins and a suite of ancestral skeletal traits, newly sequenced across two libraries.
Erpetoichthys calabaricus · Reedfish
A close relative of the bichir, also newly sequenced across two libraries, complementing the non-teleost ray-finned representation.
Atractosteus spatula · Alligator Gar
A deeply branching ray-finned fish (Holostei) newly sequenced across two libraries, forming together with bichir and reedfish a broad non-teleost ray-finned backbone for the atlas.
All 41 Fish Species
36 species in this atlas were newly sequenced; 5 were drawn from existing public datasets. The list below follows the classification in the species library table.
Newly Sequenced · 36 Species
| Common Name | Latin Name |
|---|---|
| Yellowfin seabream | Acanthopagrus latus |
| Clown anemonefish | Amphiprion ocellaris |
| Orange clownfish | Amphiprion percula |
| Climbing perch | Anabas testudineus |
| Alligator gar | Atractosteus spatula |
| Siamese fighting fish | Betta splendens |
| Snakehead | Channa argus |
| Copperband butterflyfish | Chelmon rostratus |
| White-spotted bamboo shark | Chiloscyllium plagiosum |
| Grass carp | Ctenopharyngodon idella |
| Common carp | Cyprinus carpio |
| Live sharksucker | Echeneis naucrates |
| Brown-marbled grouper | Epinephelus fuscoguttatus |
| Giant grouper | Epinephelus lanceolatus |
| Reedfish | Erpetoichthys calabaricus |
| Northern pike | Esox lucius |
| Mosquitofish | Gambusia affinis |
| Barramundi perch | Lates calcarifer |
| Zig-zag eel | Mastacembelus armatus |
| Wuchang bream | Megalobrama amblycephala |
| Boeseman's rainbowfish | Melanotaenia boesemani |
| Largemouth bass | Micropterus salmoides |
| Asian swamp eel | Monopterus albus |
| Rainbow trout | Oncorhynchus mykiss |
| Leopard coral grouper | Plectropomus leopardus |
| Guppy | Poecilia reticulata |
| Gray bichir | Polypterus senegalus |
| West African lungfish | Protopterus annectens |
| Asian arowana | Scleropages formosus |
| Turbot | Scophthalmus maximus |
| Mandarin fish | Siniperca chuatsi |
| Mandarinfish | Synchiropus splendidus |
| Yellowhead catfish | Tachysurus fulvidraco |
| Green spotted puffer | Tetraodon nigroviridis |
| Green swordtail | Xiphophorus hellerii |
| Southern platyfish | Xiphophorus maculatus |
Public Datasets · 5 Species
| Common Name | Latin Name |
|---|---|
| Mexican tetra | Astyanax mexicanus |
| Goldfish | Carassius auratus |
| Zebrafish | Danio rerio |
| Mchenga conophoros | Mchenga conophoros |
| Sea lamprey | Petromyzon marinus |
Dive Deeper
All 100 Vertebrates
Browse the complete species catalog across all lineages.
Mammals
Compare the fish backbone against the mammalian branch.
Birds and Others
Birds, reptiles and amphibians alongside the fishes.
Cell Browser
Explore fish cells interactively in the atlas.