PUBLICATION
TEMPO enables sequential genetic labeling and manipulation of vertebrate cell lineages
- Authors
- Espinosa-Medina, I., Feliciano, D., Belmonte-Mateos, C., Linda Miyares, R., Garcia-Marques, J., Foster, B., Lindo, S., Pujades, C., Koyama, M., Lee, T.
- ID
- ZDB-PUB-221124-8
- Date
- 2022
- Source
- Neuron 111(3): 345-361.e10 (Journal)
- Registered Authors
- Belmonte-Mateos, Carla, Lee, Tzumin, Pujades, Cristina
- Keywords
- CRISPR, cell cycle, cell fate, cell lineage, gliogenesis, mouse cortex, neurogenesis, zebrafish hindbrain
- MeSH Terms
-
- Animals
- Cell Differentiation/genetics
- Cell Lineage/physiology
- Gene Expression Regulation, Developmental
- Mice
- Neurogenesis/genetics
- Neuroglia
- Neurons*/physiology
- Zebrafish*
- PubMed
- 36417906 Full text @ Neuron
Citation
Espinosa-Medina, I., Feliciano, D., Belmonte-Mateos, C., Linda Miyares, R., Garcia-Marques, J., Foster, B., Lindo, S., Pujades, C., Koyama, M., Lee, T. (2022) TEMPO enables sequential genetic labeling and manipulation of vertebrate cell lineages. Neuron. 111(3):345-361.e10.
Abstract
During development, regulatory factors appear in a precise order to determine cell fates over time. Consequently, to investigate complex tissue development, it is necessary to visualize and manipulate cell lineages 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 labeling and manipulation of consecutive cell generations in vertebrates. TEMPO is based on CRISPR and powered by a cascade of gRNAs that drive orderly activation and inactivation of reporters and/or 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping