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Competing Programs Shape Cortical Sensorimotor-Association Axis Development
Jeremiah Tsyporin1, Menglei Zhang1, Cai Qi1
1Department of Neuroscience, Yale School of Medicine, New Haven, CT, USA.
Biorxiv : the Preprint Server for Biology
|July 16, 2025
Summary
The Multinodal Induction-Exclusion in Network Development (MIND) model explains how neocortical development patterns the sensorimotor-to-association (S-A) axis. Competing molecular programs of induction and exclusion shape brain networks and cognitive functions.
Area of Science:
- Neuroscience
- Developmental Biology
- Genetics
Background:
- The neocortex exhibits a sensorimotor-to-association (S-A) axis, crucial for cognition, but its developmental underpinnings are unclear.
- This axis ranges from primary sensorimotor areas to transmodal association areas supporting abstract thought.
Purpose of the Study:
- To present the Multinodal Induction-Exclusion in Network Development (MIND) model, explaining neocortical S-A axis patterning.
- To elucidate the molecular and connectional mechanisms driving this developmental process across species.
Main Methods:
- Analysis of multispecies transcriptomic and connectional data.
- Investigated molecular programs (e.g., retinoic acid, SATB2, ZBTB18) and their roles in neocortical patterning.
- Examined gene expression patterns (e.g., PLXNC1, SEMA7A) influencing connectivity.
Main Results:
- The MIND model proposes that S-A patterning results from competing induction and exclusion programs originating from different cortical regions.
- Pericentral programs, regulated by retinoic acid, spread inward, while central programs are induced by thalamocortical inputs, promoting primary areas and excluding others.
- These antagonistic processes create spatial compartmentalization and shape cortico-cortical connectivity, establishing the S-A axis topography.
Conclusions:
- The MIND model offers a unifying framework for understanding neocortical development, evolution, and clinical conditions.
- Induction and exclusion are identified as fundamental, complementary principles governing the formation of processing hierarchies in the neocortex.
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