# A New Model System for Adult Neurogenesis

> **NIH NIH R21** · HARVARD UNIVERSITY · 2022 · $247,110

## Abstract

PROJECT SUMMARY
In development and homeostasis, progenitor stem cells of critical organ systems often divide
asymmetrically. Memory formation involves adult neurogenesis, wherein progenitor stem cells in the
adult brain divide asymmetrically to produce nascent neurons. The ability to form and recall specific
memories is indispensable to our survival. Patients with neurodegenerative diseases such as
Alzheimer’s exhibit drastic disruptions in learning and memory. As such, elucidating the developmental
and mechanistic underpinnings of memory formation is critical to identifying and preventing processes
that lead to brain disease. Our long-term objective is to understand the molecular mechanisms that
generate new neurons in adult brains. We have established a new model organism for tackling this
problem, one that combines the neural complexity of a mammal with the ease of laboratory culture and
genetic manipulation of an insect: the cricket Gryllus bimaculatus. In the cricket brain, neuroblasts are
neural stem cells necessary for learning and memory. We have discovered that the conserved
transcription factor CREB, which plays a central role in animal learning and memory, regulates the
molecular organizer oskar, and that both genes are required for long term memory. We hypothesize
that Oskar and CREB direct proper asymmetric division of neuroblasts into neurons, which allows long
term memories to be established. We will test this hypothesis through pursuit of three complementary
Specific Aims. In Aim 1, we will determine whether oskar regulates adult neuroblast asymmetric cell
division. We will use CRISPR/Cas9 and RNAi to abrogate oskar expression and determine how this
affects asymmetric cell division using in situ hybridization, immunohistochemistry, and confocal
microscopy. In Aim 2, we will identify the interacting partners of Oskar within Gryllus neuroblasts. To
this end, we will assess the neural expression and long-term memory function of genes known to
interact with oskar in other cell types. We will also take an unbiased approach to identifying relevant
oskar interactors by using single cell RNA-seq to determine the complete transcriptome of neuroblasts.
In Aim 3, we will define the role of CREB in regulating neuroblast division. We will reduce CREB
expression in the adult brain and examine how CREB loss affects neuroblast asymmetric cell division.
The results of these experiments will shed light on the cellular mechanisms that regulate memory
formation, which could lead to novel approaches to ameliorate memory-related diseases.

## Key facts

- **NIH application ID:** 10452952
- **Project number:** 1R21NS127312-01A1
- **Recipient organization:** HARVARD UNIVERSITY
- **Principal Investigator:** Cassandra G Extavour
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $247,110
- **Award type:** 1
- **Project period:** 2022-05-15 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10452952

## Citation

> US National Institutes of Health, RePORTER application 10452952, A New Model System for Adult Neurogenesis (1R21NS127312-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10452952. Licensed CC0.

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