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Meister, L.

Publications and source records attributed to Meister, L..

3 recordsLinked to original sources

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

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 neurons 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.

developmental biology↗

An amphioxus neurula stage cell atlas supports a complex scenario for the emergence of vertebrate head mesoderm

The emergence of new structures can often be linked to the evolution of novel cell types that follows the rewiring of developmental gene regulatory subnetworks. Vertebrates are characterized by a complex body plan compared to the other chordate clades and the question remains of whether and how the emergence of vertebrate morphological innovations can be related to the appearance of new embryonic cell populations. We already proposed, by studying mesoderm development in the cephalochordate amphioxus, a scenario for the evolution of the vertebrate head mesoderm. To further test this scenario at the cell population level, we used scRNA-seq to construct a cell atlas of the amphioxus neurula, stage at which the main mesodermal compartments are specified. Our data allowed us to confirm the presence of a prechordal-plate like territory in amphioxus, and shows that cell populations of the anteriormost somites and of the ventral part of the somites present a transcriptomic profile supporting the homology with vertebrate cranial/pharyngeal and lateral plate mesoderm. Finally, our work provides evidence that the appearance of the specific mesodermal structures of the vertebrate head was associated to both segregation of pre-existing cell populations, and co-option of new genes for the control of myogenesis.

evolutionary biology↗

Hindbrain rhombomere centers harbor a heterogenous population of dividing progenitors which rely on Notch-signaling

Tissue growth and morphogenesis are interrelated processes, whose tight coordination is essential for the production of different cell fates and the timely precise allocation of stem cell capacities. The zebrafish embryonic brainstem, the hindbrain, exemplifies such coupling between spatiotemporal cell diversity acquisition and tissue growth, as the neurogenic commitment is differentially distributed over time. Here, we combined cell lineage and in vivo imaging approaches to reveal the emergence of different specific cell population properties within the very same rhombomeres, and focused on the hindbrain rhombomere centers. We studied the molecular identity of rhombomere centers, and showed that they harbor different progenitor capacities that change over time. By clonal analysis, we revealed that cells within the rhombomeres decrease the proliferative capacity over time to remain mainly in G1-phase. Proliferating progenitors give rise to neurons by asymmetric and symmetric neurogenic divisions, while maintaining the pool of progenitors. The proliferative capacity of these cells differs from their neighbors, and they are delayed in the onset of Notch-activity. By functional studies we demonstrated that they rely on Notch3-signaling to be maintained as non-committed progenitors. In this study we show that cells in rhombomere centers might share steps of a similar program, despite the neurogenic asynchrony from the rhombomere counterparts, to ensure proper tissue growth.

developmental biology↗