Multimodal cell lineage reconstruction in the hindbrain reveals a link between progenitor origin and activity patterning

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Abstract

ABSTRACT Does the stem cell origin impact how daughter neurons acquire functional characteristics and assemble into circuits? Here, by multimodal cell lineage reconstruction in the zebrafish hindbrain we related a neuron’s embryonic origin to its future terminal differentiation features, such as neurotransmitter identity, and neuronal activity pattern. Intersectional lineage tracing, new developed computational tools, and genetic knockouts revealed that different progenitors formed functionally distinct neuron subtypes and could not compensate for the loss of adjacent progenitor pools, indicating developmental hardwiring. Dynamics of neuronal production suggest that progenitor competence changes over time. Whereas neurog1 -expressing progenitors contributed to both glutamatergic and GABAergic lineages at early embryonic stages, later, other progenitor pools also assumed this role. Whole-hindbrain 3D atlases combining calcium imaging to monitor spontaneous neuronal activity, with genetic perturbations and progenitor origin information, unveiled that the emergence of neuronal activity patterns was presaged by their progenitor origins. This reveals a link between cell ontogeny and neuronal activity in the zebrafish hindbrain.
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ABSTRACT Does the stem cell origin impact how daughter neurons acquire functional characteristics and assemble into circuits? Here, by multimodal cell lineage reconstruction in the zebrafish hindbrain we related a neuron’s embryonic origin to its future terminal differentiation features, such as neurotransmitter identity, and neuronal activity pattern. Intersectional lineage tracing, new developed computational tools, and genetic knockouts revealed that different progenitors formed functionally distinct neuron subtypes and could not compensate for the loss of adjacent progenitor pools, indicating developmental hardwiring. Dynamics of neuronal production suggest that progenitor competence changes over time. Whereas neurog1-expressing progenitors contributed to both glutamatergic and GABAergic lineages at early embryonic stages, later, other progenitor pools also assumed this role. Whole-hindbrain 3D atlases combining calcium imaging to monitor spontaneous neuronal activity, with genetic perturbations and progenitor origin information, unveiled that the emergence of neuronal activity patterns was presaged by their progenitor origins. This reveals a link between cell ontogeny and neuronal activity in the zebrafish hindbrain. Competing Interest Statement The authors have declared no competing interest. Footnotes ↵4 Lead contact We included the videos and some Supplementary Data

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last seen: 2026-05-20T01:45:00.602351+00:00