The protomap is propagated to cortical plate neurons through an Eomes-dependent intermediate map

Area of Science:

• Neuroscience
• Developmental Biology
• Genetics

Background:

• The initial patterning of the cortical area map relies on transcription factor (TF) gradients in the neocortical primordium, establishing a "protomap" in the embryonic ventricular zone (VZ).
• Mechanisms for propagating regional identity from VZ progenitors to cortical plate (CP) neurons remain largely unknown.

Purpose of the Study:

• To investigate the mechanisms that propagate regional identity from the embryonic ventricular zone (VZ) to cortical plate (CP) neurons.
• To elucidate the role of transcription factors, specifically Eomes (Tbr2), in shaping distinct molecular maps within the developing neocortex.

Main Methods:

• Analysis of gene expression gradients in radial glia progenitors, intermediate progenitors, and projection neurons across the VZ, subventricular zone (SVZ), and CP.
• Inactivation of the Eomes (Tbr2) transcription factor to assess its impact on gene expression and axonal projections.
• Tracing the Pax6 → Eomes → Tbr1 transcription factor cascade.

Main Results:

• Distinct molecular maps of regional identity exist in the VZ, SVZ, and CP, reflecting different gene expression gradients.
• Eomes (Tbr2) modulates the "intermediate map" in the SVZ.
• Eomes inactivation led to rostrocaudal shifts in SVZ and CP gene expression, altering axonal projections (loss of corticospinal, gain of corticotectal).

Conclusions:

• Cortical areas and connections are shaped by sequential maps of regional identity, propagated by the Pax6 → Eomes → Tbr1 transcription factor cascade.
• Dysregulation of PAX6, EOMES, and TBR1 is implicated in human neurodevelopmental disorders like intellectual disability and autism.