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Belmonte-Mateos, C.

Publications and source records attributed to Belmonte-Mateos, C..

2 recordsLinked to original sources

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↗

TEMPO: A system to sequentially label and genetically manipulate vertebrate cell lineages

During development, regulatory factors appear in a precise order to determine cell fates over time. To investigate complex tissue development, one should not just label cell lineages but further visualize and manipulate cells with temporal control. Current strategies for tracing vertebrate cell lineages lack genetic access to sequentially produced cells. Here we present TEMPO (Temporal Encoding and Manipulation in a Predefined Order), an imaging-readable genetic tool allowing differential labelling and manipulation of consecutive cell generations in vertebrates. TEMPO is based on CRISPR and powered by a cascade of gRNAs that drive orderly activation/inactivation of reporters/effectors. Using TEMPO to visualize zebrafish and mouse neurogenesis, we recapitulated birth-order-dependent neuronal fates. Temporally manipulating cell-cycle regulators in mouse cortex progenitors altered the proportion and distribution of neurons and glia, revealing the effects of temporal gene perturbation on serial cell fates. Thus, TEMPO enables sequential manipulation of molecular factors, crucial to study cell-type specification. One-Sentence SummaryGaining sequential genetic access to vertebrate cell lineages.

developmental biology↗