# Regulation of directed neuroblast migration by the ECM and MAB-5/Hox

> **NIH NIH R01** · UNIVERSITY OF KANSAS LAWRENCE · 2020 · $350,819

## Abstract

Project Summary
Directed cell migration is a fundamental morphogenetic mechanism used by animals to build tissues and
organs. For example, neural crest cells migrate long distances in the embryo and develop into a plethora of cell
types, including the entire peripheral nervous system. In C. elegans, the Q cells are bilateral neuroblasts born
in the posterior-lateral region of the animal that undergo left-right asymmetric migration. Initially, QR on the
right protrudes and migrates anteriorly, and QL on the left posteriorly. This initial directed migration is regulated
by the receptor molecules UNC-40/DCC and PTP-3/LAR, which drive posterior migration. A left-right (L/R)
asymmetry in the Q cells results in UNC-40 and PTP-3 being active in QL but not QR, leading to posterior
versus anterior migration, respectively. The second phase of migration relies on Wnt signaling and begins after
the first Q cell division. QL and descendants encounter a posterior EGL-20/Wnt signal that drives expression of
the MAB-5/Hox transcription factor, whereas QR and descendants do not express MAB-5. Further posterior
migration of the QL descendants requires MAB-5, which is both necessary and sufficient for posterior Q
descendant migration. QL and QR undergo an identical pattern of cell division, migration and cell death to
generate three neurons apiece. The phases of Q migration are independent (e.g. in mab-5 mutants, QL initial
migration to the posterior is normal, but Q descendants then migrate anteriorly).
Our preliminary data indicate that an inherent L/R asymmetry in QL versus QR determines how these cells
respond to the extracellular matrix (ECM), which specifies anterior versus posterior migration. Specifically, the
Collagenα1XXIV molecule DPY-17 directs posterior migration. DPY-17 is expressed broadly throughout the
animal, as opposed to other ECM-related guidance cues (UNC-6/Netrin, SLT-1/Slit) expressed in specific
regions to direct migration. Possibly, the structure of the ECM itself provides anterior-posterior guidance
information to the Q cells, and UNC-40/DCC and PTP-3/LAR interpret this information. We will test this idea by
analyzing DPY-17 and other ECM components in initial Q migration. After initial migration, mab-5/Hox
expression in QL directs posterior migration. mab-5/Hox is a terminal selector gene which specifically controls
posterior migration and not other aspects of cell division, death, or neuronal differentiation. We will take a
functional-genomic approach to define a transcriptional cassette downstream of the MAB-5/Hox terminal
selector that directs posterior migration. This proposal utilizes a cutting-edge combination of techniques (e.g.
fluorescence-activated cell sorting (FACS) of C. elegans cells and RNA-seq), and leverages the strengths of
the C. elegans system in discovery science. It has the potential to significantly advance the goal of achieving a
detailed understanding of a simple developmental decision to migrate posteriorly vers...

## Key facts

- **NIH application ID:** 10072659
- **Project number:** 1R01NS115467-01A1
- **Recipient organization:** UNIVERSITY OF KANSAS LAWRENCE
- **Principal Investigator:** Erik A Lundquist
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $350,819
- **Award type:** 1
- **Project period:** 2020-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10072659

## Citation

> US National Institutes of Health, RePORTER application 10072659, Regulation of directed neuroblast migration by the ECM and MAB-5/Hox (1R01NS115467-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10072659. Licensed CC0.

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