Molecular and functional definition of the developing human striatum

Area of Science:

• Neuroscience
• Developmental Biology
• Genomics

Background:

• Human brain complexity arises from intricate molecular programming during development.
• Understanding prenatal gene expression is crucial for deciphering neuronal specification.

Purpose of the Study:

• To systematically investigate gene expression changes in the prenatal human striatum and cerebral cortex.
• To identify molecular factors distinguishing striatal from neocortical neuronal identities.
• To compare human striatal development with that of model organisms.

Main Methods:

• Analysis of gene expression in human brain tissue from post-conception weeks 2 to 20.
• Identification of tissue-specific gene coexpression networks and differentially expressed genes.
• Protein-level monitoring of developmental determinants and in vitro electrophysiological profiling of human striatal neurons.

Main Results:

• Discovery of tissue-specific gene coexpression networks and key distinguishing genes, including transcription factors.
• Identification of a minimal set of bimodal genes critical for regional identity.
• Uncovered unexpected differences compared to mouse striatal development.
• Characterized regional expression patterns and refinement of 36 developmental determinants at the protein level.
• Demonstrated refined molecular and functional properties of in vitro differentiated human striatal neurons.

Conclusions:

• Gene expression patterns provide a blueprint for human striatal and neocortical neuron specification.
• Transcriptional and functional processes converge to define distinct neuronal cell types during development.
• This study offers a valuable resource for understanding human brain development and associated disorders.