# Coordination of projection neuron fate and position by let-7

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2023 · $422,449

## Abstract

Project Summary:
The central nervous system contains a myriad of different cell types that receive and integrate information from
the environment to generate the appropriate biological responses. Failure to produce the right composition of
neuronal subtypes or defects in their localization can result in several mental and physical conditions that range
from cognitive disorders to severe brain malformations. In the neocortex, a specialized pool of multipotent cells
-called radial glial cells- gives rise to all the different populations of projection neurons in a conserved sequence.
Importantly, early born projections neurons localize at the apical side of the cortical plate whereas later born
neurons localize atop of their predecessors. Despite the strong correlation between projection neuron fate
identity and position, the molecular mechanisms involved in such correlation remain elusive. MicroRNAs
(miRNAs) have recently been uncovered as strong cell fate determinants and we and others have shown that
let-7 expression in radial glia cells promotes the neurogenesis of late born cortical projection neurons.
Importantly, we further demonstrate that let-7 expression positive correlates with projection neuron location in
upper cortical layers (i.e., closer to the pial surface). Our preliminary data show that let-7 regulates neuron
migration by opposing the expression of Rbx2, a core member of the E3 ubiquitin ligase CRL5, previously
identified as a key factor to end projection neuron migration. Thus, we hypothesize that elevated expression of
let-7 in late-born projection neurons reduces the activity of CRL5, promoting neuron migration. The proposed
research will identify let-7 as the first coordinator of neural progenitor competence and projection neuron
migration/localization, and unveil its molecular mechanism of action.

## Key facts

- **NIH application ID:** 10722629
- **Project number:** 1R21NS133564-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Anna La Torre
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $422,449
- **Award type:** 1
- **Project period:** 2023-06-15 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10722629

## Citation

> US National Institutes of Health, RePORTER application 10722629, Coordination of projection neuron fate and position by let-7 (1R21NS133564-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10722629. Licensed CC0.

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