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Neurulation

Neurulation

Neurulation is the embryological process which forms the precursors of the central nervous system and occurs after gastrulation has established the three primary cell layers of the embryo: ectoderm, mesoderm, and endoderm. In humans, the majority of this system is formed via primary neurulation, in which the central portion of the ectoderm—originally appearing as a flat sheet of cells—folds upwards and inwards, sealing off to form a hollow neural tube. As development proceeds, the...

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The CTNNBIP1-CLSTN1 fusion transcript regulates human neocortical development.

Min-Yi Ou¹, Qi Xiao², Xiang-Chun Ju³

¹School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; Institute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, China.

|June 30, 2021

Summary

Fusion transcripts play a key role in human brain development. This study identified novel fusion RNAs, including CTNNBIP1-CLSTN1, influencing neural progenitor cells and Wnt/β-catenin signaling, impacting cortex growth and evolution.

Keywords:

CTNNBIP1-CLSTN1 Wnt/β-catenin signaling basal neural progenitor cortical expansion fusion transcript neurogenesis outer radial glia

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Live Imaging of Mitosis in the Developing Mouse Embryonic Cortex

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Area of Science:

Neuroscience
Genetics
Developmental Biology

Background:

Fusion transcripts are found in human tissues but their role in brain development is unknown.
The developing neocortex is crucial for higher cognitive functions.

Purpose of the Study:

To investigate the function of fusion transcripts during human brain development.
To identify specific fusion transcripts involved in neural progenitor cell regulation and cortical patterning.

Main Methods:

Analysis of RNA-sequence libraries from early to middle embryonic stages.
Focus on CTNNBIP1-CLSTN1 (CTCL) fusion transcript in neural progenitors.
Utilized human cerebral organoid models to study CTCL function.

Main Results:

Identified 1,055 fusion transcripts in the developing neocortex.
Discovered 98 fusion transcripts with distinct expression in neural progenitors and neurons.
CTCL is enriched in outer radial glial cells and its downregulation impairs neural progenitor proliferation and promotes precocious neuronal differentiation.
CTCL expression modulates Wnt/β-catenin signaling, affecting cortex patterning.

Conclusions:

Fusion transcripts play significant roles in human brain development and evolution.
CTNNBIP1-CLSTN1 is a key fusion transcript regulating neural progenitor dynamics and cortical development.
Findings provide insights into the genetic mechanisms underlying human cortical expansion.