DMRT5 Together with DMRT3 Directly Controls Hippocampus Development and Neocortical Area Map Formation

Area of Science:

• Neuroscience
• Developmental Biology
• Genetics

Background:

• The cerebral cortex exhibits complex patterning, with specific regions like the cortical hem acting as crucial signaling centers.
• The role of specific transcription factors in directing neocortical area map formation remains an active area of research.

Purpose of the Study:

• To investigate the function of the Dmrt5 gene in neocortical patterning.
• To determine if Dmrt5 acts independently of the cortical hem in regulating the neocortical area map.
• To elucidate the relationship between Dmrt5 and Dmrt3 in cortical development.

Main Methods:

• Utilized conditional Dmrt5 gain and loss of function mouse models.
• Analyzed changes in neocortical area maps and cortical patterning.
• Examined Dmrt5 and Dmrt3 expression patterns and regulatory interactions.

Main Results:

• Constitutive Dmrt5 null mice displayed cortical patterning abnormalities, including loss of the cortical hem.
• Conditional Dmrt5 manipulation altered the neocortical area map without affecting the hem, indicating DMRT5's independent role.
• Dmrt5 deletion impacted hippocampal size and the neocortical/paleocortical boundary.
• Dmrt3 deficiency caused milder patterning defects, with Dmrt5 expression increasing in its absence.
• DMRT5 upregulates Dmrt3 and negatively autoregulates itself, stabilizing DMRT5 levels.

Conclusions:

• DMRT5 is a key transcription factor directing the rostral-to-caudal pattern of the neocortical area map, independent of the cortical hem.
• DMRT5 and DMRT3 act in concert, with precisely regulated levels, to control cerebral cortex patterning.
• These findings identify DMRT5 as a critical regulator of neocortical area size and position.