# Adhesion-GPCRs:  Regulators of dendritic development, synaptogenesis and mental health

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2020 · $396,250

## Abstract

PROJECT SUMMARY
Dendrites exhibit immense diversity in their macrostructure (arbors), which stipulates the availability of a
neuron to circuits and its computational properties, and microstructure (dendritic spines), which dynamically
support and shape synaptic function. Arbor and spine/synapse development must be coordinated to form
functional dendrites. Though synaptic activity plays a crucial role, the heterogeneity of developmental
responses to activity indicates that other mechanisms are required. In this proposal, we will test the hypothesis
that the adhesion G-protein coupled receptor (A-GPCR) brain-specific angiogenesis inhibitor 1 (BAI1/
ADGRB1) coordinates dendritic arbor and spine development through differential activation of multiple
signaling pathways. This hypothesis is based on our published and preliminary data showing: (i) that BAI1
mediates growth arrest of dendritic arbors via a novel pathway coupling to the Rho-family small GTPase RhoA;
(ii) that BAI1 promotes excitatory synaptogenesis in cortical and hippocampal neurons via the Rho-family small
GTPase Rac1 and trans-synaptic signaling; and (iii) that BAI1 differentially affects dendrite development in an
age-dependent manner and that altering BAI1 configuration has age-dependent effects on downstream
signaling pathways. We propose a multidisciplinary approach to define the roles of BAI A-GPCRs in regulating
and coordinating dendritic arbor and spine/synapse development utilizing in vivo and cultured neurons, genetic
models, molecular replacement, live imaging with fluorescent reporters, mixed culture assays, biochemistry
and electrophysiology. The pathways that we are defining include proteins implicated in treatment-resistant
bipolar disorder (Bcr), autism spectrum disorder (neuroligin-1 and IRSp53), and schizophrenia (BAI3). Thus,
success of this proposal will not only provide material advances in the study of dendrite development and
synaptogenesis, but also test a novel and powerful hypothesis regarding the coordination of these processes
and provide new therapeutic targets against widespread human mental diseases.

## Key facts

- **NIH application ID:** 9855086
- **Project number:** 5R01MH109511-04
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Kimberly R Tolias
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $396,250
- **Award type:** 5
- **Project period:** 2017-03-08 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9855086

## Citation

> US National Institutes of Health, RePORTER application 9855086, Adhesion-GPCRs:  Regulators of dendritic development, synaptogenesis and mental health (5R01MH109511-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9855086. Licensed CC0.

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