# Regulation of neural migration during brain development

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA RIVERSIDE · 2021 · $330,935

## Abstract

The proposed studies will identify mechanisms through which Cas adaptor proteins regulate cortical
development and function. Accurate cell migration and lamination are indispensable for the development of a
functional nervous system. Congenital disruption of any of these processes can result in neurodevelopmental
disorders ranging from lissencephaly to autism-spectrum disorders. During multiple developmental steps,
neurons are guided by repulsive and attractive cues, while actively interacting with the extracellular matrix
(ECM) and other cells. Although much is known about the ligand-receptor pairs required for these cues to
regulate cell trajectories, it remains unknown how instructive and adhesive cues are integrated and interpreted
within the neuron. The Cas (Crk associated substrate) family of cytosolic adaptor proteins are known to signal
downstream of several neural guidance cues, and regulate focal adhesion turnover. Using Cas proteins as a
model, we have a unique opportunity to broaden our understanding of how instructive and permissive signaling
pathways converge during neural development to regulate cell adhesion. To test the hypothesis that Cas
proteins are essential for coordinating cortical lamination and migration, experiments will be organized into
three Specific Aims. Guided by strong preliminary data showing that ablation of Cas genes results in cortical
defects that resemble cobblestone lissencephaly, Aim 1 will establish, for the first time, the functional
requirement for Cas proteins during cortical migration and lamination. Aim 2 will explore the contributions of
Cas-mediated cortical scaffold formation to physiology and behavior, using EEG and behavioral approaches.
Aim 3 will test how regulation of Cas function affects cortical lamination. These experiments will provide new
knowledge on the basic mechanisms underlying the establishment of neural circuits essential for perception
and cognition.

## Key facts

- **NIH application ID:** 10116497
- **Project number:** 5R01NS104026-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA RIVERSIDE
- **Principal Investigator:** Martin Miguel Riccomagno
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $330,935
- **Award type:** 5
- **Project period:** 2018-06-15 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10116497

## Citation

> US National Institutes of Health, RePORTER application 10116497, Regulation of neural migration during brain development (5R01NS104026-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10116497. Licensed CC0.

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