Illumination of neural development by in vivo clonal analysis

Abstract

Single embryonic and adult neural stem cells (NSCs) are characterized by their self-renewal and differentiation potential. Lineage tracing via clonal analysis allows for specific labeling of a single NSC and tracking of its progeny throughout development. Over the past five decades, a plethora of clonal analysis methods have been developed in tandem with integration of chemical, genetic, imaging and sequencing techniques. Applications of these approaches have gained diverse insights into the heterogeneous behavior of NSCs, lineage relationships between cells, molecular regulation of fate specification and ontogeny of complex neural tissues. In this review, we summarize the history and methods of clonal analysis as well as highlight key findings revealed by single-cell lineage tracking of stem cells in developing and adult brains across different animal models.

Cascade diversification directs generation of neuronal diversity in the hypothalamus

“…To investigate whether neuronal diversity originates from individual RGCs, we set out to develop a single-cell lineage-tracing system in the mouse hypothalamus. Our previous reports demonstrated that MADM (mosaic analysis with double markers) reporter mice in combination with CreER T2 driver mice are a genetic tool for spatially and temporally specific clonal analysis of dividing neural progenitors (Wong et al, 2018;Xu et al, 2018).…”

A Spacetime Odyssey of Neural Progenitors to Generate Neuronal Diversity

“…1A). Albeit many results from transplantation experiments, retroviral lineage tracing, genetic fate mapping, and in vivo clonal analysis point toward the hypothesis of multipotent progenitors with strict temporal coding [17][18][19][20][21], it is still possible that a majority of multipotent NPCs coexist with a minority of fate-specified progenitors that remain to be identified. More importantly, both hypotheses support the predetermined model in which the fate of cortical progenitors is pre-specified to produce projection neurons by either a temporal code or an inherent genetic program.…”

“…It is also unclear how deterministic and stochastic factors shape the cascade diversifying trajectory during lineage progression. Single-cell lineage tracing by integrating an inducible barcoding approach with transcriptomic data may be able to systematically record the developmental trajectory of each individual NPC [ 21 ].…”