Bibliography:

📖 Numbers correspond to the citations in the original paper. Full references omitted for brevity.

🌱💡 Take-home message:
Microbiome components can shape host phenotypes and be subject to natural selection independently of host genome changes.
Thus, microbiome can act as a non-nuclear mechanism contributing to adaptation to environmental changes.

Tryptophan metabolism links gut microbes to brain function⁶⁷ via AhR signaling⁶⁸–⁷⁰, affecting the CNS⁷¹–⁷².
🐝Lactobacillus is associated with behavior⁵⁶–⁵⁸,⁷³–⁷⁵ and memory in bees⁷⁶.
Their data suggest that Lactobacillus → tryptophan metabolism → ILA modulates activity behavior⁷⁷.

🧠 Results:

Selection on low-activity donors + microbiome transference:

⬇️ Mice locomotor activity over generations
⬇️ Lactobacillus spp. and circulating ILA

Follow-up tests show that Lactobacillus johnsonii and ILA independently reduce activity, recapitulating the selected-line phenotype⁷⁹.

🧪 What they did:

They applied selection on a behavioral trait (low activity) and transferred the gut microbiome to germ-free mice over multiple “generations” via fecal transmission through coprophagy, thereby studying microbiome-mediated host traits independently of host genetic changes.

Same genotype ≠ same phenotype when microbes differ in aphids⁹–¹². In vertebrates, can microbiomes generate phenotypic variation subject to natural selection?¹³,¹⁴ Many gut-microbes are inherited vertically in primates and other vertebrates²⁹–³¹, with long-term codiversification³²–³⁵.

🦠 Host-associated microbiomes can influence host development, ecological niches, and even evolutionary trajectories¹–⁷. However, teasing host-genetic vs microbial effects is a challenging matter.

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5. Giliberti A et al. 2020, Eur J Med Genet 63:103627, doi.org/10.1016/j.ej...

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📚 Meis2 is an evolutionarily conserved architect of the vertebrate brain — orchestrating regional patterning, neuronal differentiation, and circuit assembly. Its persistence in the hindbrain underscores its key role in development, evolution, and potential therapy for neurodevelopmental disorders.

🔬 Beyond this difference, Meis2 preserves its expression across the hypothalamus, optic tectum, cerebellar nuclei, and hindbrain rhombomeres (r1–r3), revealing a conserved molecular blueprint shaping vertebrate brain evolution.

🧠During Xenopus laevis brain development, Meis2 expression defines ventropallial and pallidal territories (septal groups, BNST) but is almost absent from the striatum — a clear contrast with mammals that hints at evolutionary divergence in cell specification.

🐸 Studying Meis2 in Xenopus laevis is key because its clearly segmented brain allows precise mapping of neuroanatomical boundaries.

👉 Xenopus, as an anamniote tetrapod, bridges zebrafish and amniotes, letting us explore how neuronal specification is conserved or diversified across vertebrates.

🔬 Meis2 is a key transcription factor in neurogenesis: it cooperates with Pax6 in dopaminergic neuron differentiation 1-2, regulates progenitor proliferation 3-4, patterns forebrain & hindbrain, and mutations cause intellectual disability & cardiac defects 5.

11. Atoji Y, Sarkar S & Wild JM 2016, Hippocampus 26(12):1608–1617, doi.org/10.1002/hipo...

9. Applegate MC, Gutnichenko KS & Aronov D 2023, J Comp Neurol 531(16):1669–1688, doi.org/10.1002/cne....
10. Applegate MC, Gutnichenko KS, Mackevicius EL & Aronov D 2023, Curr Biol 33(12):2465–2477e2467, doi.org/10.1016/j.cu...

7. Guyonnet AEM, Racicot KJ, Brinkman B & Iwaniuk AN 2025, Brain Struct Funct 230(1):9, doi.org/10.1007/s004...
8. Rook N, Stacho M, Schwarz A, Bingman VP & Güntürkün O 2023, J Comp Neurol 531(7):790–813, doi.org/10.1002/cne....

4. Rehkämper G, Haase E & Frahm HD 1988, Brain Behav Evol 31:141–149
5. Rehkämper G, Frahm HD & Cnotka J 2008, Brain Behav Evol 71(2):115–126, doi.org/10.1159/0001...
6. Ebinger P & Löhmer R 1984, Z Zool Syst Evolut-forsch 22:136–145.

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1. Wallraff HG 2005, Avian navigation: pigeon homing as a paradigm, Springer, Berlin Heidelberg.
2. Bingman VP 2018, J Exp Biol 221:jeb163089, doi.org/10.1242/jeb....
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