# Molecular Mechanisms of Dendrite Formation During Embryonic Neuronal Development

> **NIH NIH R56** · STATE UNIVERSITY NEW YORK STONY BROOK · 2020 · $392,153

## Abstract

An early and essential event in mammalian embryonic brain development is neuronal polarization, in which
distinct axonal and dendritic compartments are formed that inherently differ in their molecular composition.
These differences underlie the unique morphology and function of these compartments, and are responsible
for directed information flow in the brain. Aberrations in neuron polarization lead to developmental
neuropathologies, intellectual disability, epilepsy, neuropsychiatric and autism spectrum disorders. Bipolar
polarity establishment in neocortical and hippocampal CA1 Pyramidal neuron progenitors marks axon/apical
dendrite polarity - the apical dendrite will develop from the leading process whereas the trailing process will
become the axon. Specification of the axon has dominated studies on neuron polarization, yielding an
understanding of the mechanisms underlying axonal identity, its specification and growth. Much effort has also
been directed towards elucidation of the mechanisms that control later events in dendrite morphogenesis - growth, branching, and structural plasticity. However, the events leading to bipolar polarity and the subsequent
development of the apical dendrite, remain elusive. We propose that distinctly higher cyclic GMP (cGMP)
generated via localized assembly of a cGMP production machinery at the leading edge of developing
pyramidal neurons, promotes bipolar polarity, leading process formation, and apical dendrite development.
Using state of the art lifetime decay FLIM-FRET cGMP measurements in mouse developing pyramidal neurons
in acute slice, combined with cutting edge genetic approaches, and localized optogenetic manipulations of
cGMP production, this study is designed to determine the spatio-temporal regulation of cGMP during polarity
establishment and apical dendrite development and to identify its mechanistic basis in developing pyramidal
neurons in vivo. These studies will provide important advance in the understanding of the early molecular
events that take place during axon/apical dendrite development in principal excitatory neurons in the rodent
brain.

## Key facts

- **NIH application ID:** 10129449
- **Project number:** 2R56NS084111-06A1
- **Recipient organization:** STATE UNIVERSITY NEW YORK STONY BROOK
- **Principal Investigator:** Maya Shelly
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $392,153
- **Award type:** 2
- **Project period:** 2014-01-15 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10129449

## Citation

> US National Institutes of Health, RePORTER application 10129449, Molecular Mechanisms of Dendrite Formation During Embryonic Neuronal Development (2R56NS084111-06A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10129449. Licensed CC0.

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