# Understanding the Developmental Mechanisms that Ensure Robustness in Neuronal Patterning

> **NIH NIH R00** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $160,518

## Abstract

Abstract: Establishing a balance between the activities of competing neuronal circuits is essential to the
coordination of behaviors. We propose to investigate the developmental strategies that ensure the
establishment of this balance in the nervous system. Studies of the vertebrate embryonic nervous system have
shown that correlated activity patterns the structure and output nascent circuits through mechanisms akin to
learning. The scale and complexity of vertebrate brains has made it challenging to identify the rules which
govern this learning or the mechanisms which drive optimization of the circuit toward a balanced output. The
small size and invariance of the Caenorhabditis elegans nervous system make it possible to study these
processes with specificity not possible in vertebrates. Using the development of one of the first functional
circuits in the C. elegans embryo as a model, I will study how functional balance is established in the
developing nervous system and identify the developmental mechanisms that ensure the robustness of this
balance. To accomplish this goal, I propose the following specific aims: 1) To identify the models of IL1 neuron
function in the patterning of embryonic head movement. 2) To automate and improve an approach for
controlling transgene expression with single cell resolution by infrared laser-induced heatshock. And 3) To
determine the mechanisms by which the IL1 circuit establishes and maintains a balanced output to produce
coordinated movements. To enable this, I have developed a real-time cell tracking system which automates
the identification of targeted cells during embryonic development and can control the conduct of single cell
optical perturbations such as laser ablation as described in a recently published paper in Developmental
Cell or, as will be developed in Aim 2, single cell heatshock. I have also developed an automated image
analysis pipeline which allows me to track and measure movement patterns in the early embryo with which I
have identified the neuronal origins of patterned head movement and, using genetic mutants of neuronal
function, shown that this patterning is defined by neuronal input. I believe that this work will provide important
insights into the patterning of the embryonic nervous system with implications for our understanding of the
circuit-level origins of some neurodevelopmental disorders. In order to expand my training as a biologist and
complement my broad technical training and expertise, I will carry out the mentored phase of this award as a
postdoctoral Research Associate in the laboratory of Dr. Zhirong Bao, an expert on C. elegans embryonic
development, and under the mentorship of a well-accomplished advisory committee comprised of experienced
biologists and neuroscientists. I have designed a structured plan to further my scientific training and support
my career development to prepare for an independent career. The Sloan Kettering Institute and the tri-
institutional commu...

## Key facts

- **NIH application ID:** 10009409
- **Project number:** 5R00HD096050-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Pavak Kirit Shah
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $160,518
- **Award type:** 5
- **Project period:** 2019-09-30 → 2022-09-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10009409

## Citation

> US National Institutes of Health, RePORTER application 10009409, Understanding the Developmental Mechanisms that Ensure Robustness in Neuronal Patterning (5R00HD096050-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10009409. Licensed CC0.

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