Human NDE1 splicing and mammalian brain development

Area of Science:

• Evolutionary biology
• Neuroscience
• Genetics

Background:

• Understanding human brain uniqueness requires exploring genetic and molecular differences with related species.
• Nuclear distribution factor E-homolog 1 (NDE1) is implicated in human brain evolution and neurogenesis.
• The evolutionary changes in NDE1, particularly its splicing, remain largely uninvestigated.

Purpose of the Study:

• To investigate the evolutionary changes in NDE1 gene structure and splicing.
• To identify the regulatory elements controlling NDE1 terminal exon choice.
• To understand the role of alternative splicing in NDE1's contribution to human brain evolution.

Main Methods:

• Comparative analysis of NDE1 gene structure between human and mouse.
• Chimeric minigenes splicing assays to study terminal exon selection.
• Investigation of cis and trans acting regulatory signals.

Main Results:

• NDE1 exhibits different gene structures in humans and mice, leading to distinct splicing isoforms.
• Human NDE1 utilizes terminal exon 9, absent in rodents, which use exon 8T.
• Terminal exon selection is cell-dependent and influenced by the gain/loss of splicing regulatory sequences.

Conclusions:

• Evolutionary alterations in cis and trans acting signals are crucial for species-specific NDE1 splicing isoforms.
• Alternative splicing plays a significant role in human genome evolution.
• NDE1 alternative splicing may contribute to human cognitive evolution and predominance.