Developmental programming and lineage branching of early human telencephalon

The EMBO Journal, 2021 · DOI: 10.15252/embj.2020107277 · Published: September 24, 2021

Simple Explanation

This study investigates how different types of neurons are created in the early developing human brain (telencephalon). It uses advanced techniques to map out the process by which stem cells transform into specific neurons. The research indicates that both the dorsal (top) and ventral (bottom) parts of the telencephalon follow a similar pattern where stem cells become intermediate cells and then early neurons. A protein called ASCL1 is important for the first step in both regions. The study also found that the main types of neurons are determined early on, but diversity is increased during neuron creation and integration into brain circuits.

Study Duration

Not specified

Participants

Human embryonic brains from normal aborted fetuses

Evidence Level

Level: Not specified, Study type: scRNA-seq and in vitro experiments

Key Findings

1
Dorsal and ventral telencephalons share common developmental programs during neurogenesis, following a conserved trajectory from radial glial cells (RGs) to intermediate progenitor cells (IPCs_div) and then to early neuroblasts (eNBs).
2
The transcription factor ASCL1 plays a crucial role in promoting the transition from RGs to IPCs_div in both dorsal and ventral regions of the telencephalon.
3
Major neuronal fates are predetermined during dorsoventral regionalization, with neuronal diversity further shaped during neurogenesis and neural circuit integration.

Research Summary

The study reveals a conserved developmental map of the human telencephalon, highlighting the temporal cell fate transition from neuroectoderm (NE) to radial glial cells (RGs) to intermediate progenitor cells (IPCs_div), and then to early neuroblasts (eNBs). ASCL1 is identified as a key regulator in the transition from RGs to IPCs_div in both dorsal and ventral telencephalic progenitors, indicating a shared developmental program in these regions. The research also suggests that regional patterning is the primary branching point for generating distinct RGs, while a secondary branching point occurs during the transition from cycling IPCs_div to postmitotic eNBs, further diversifying neuronal populations.

Practical Implications

Therapeutic Development

Provides insights for generating specific neuronal subtypes for cell replacement therapy.

Disease Modeling

Offers a roadmap for understanding and modeling neurodevelopmental disorders.

Drug Discovery

Identifies molecular targets for manipulating progenitor proliferation and differentiation.

Study Limitations

1
The study uses embryonic brain samples, which may not fully represent later stages of development.
2
In vitro differentiation may not completely replicate in vivo processes.
3
Further studies are needed to fully understand the functional consequences of ASCL1 in human telencephalon development.

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