# Meander tail and development of the anterior lobe.

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2024 · $197,500

## Abstract

Project Summary
The anterior lobe of the cerebellum has unique sensitivities in developmental and
degenerative disorders. How anterior and posterior compartments are differentiated
developmentally are not adequately understood. The classical mouse mutation meander
tail (mea) causes both the kinked tail for which it is named and a compartment-specific
disorganization of the anterior cerebellum. Three independent alleles have been reported.
Positional cloning efforts more than a decade ago identified a genomic interval but failed
to identify causal variants due to technical limitations. Data from that project and from
genome-scale mutagenesis projects highly suggest a recurrent regulatory mutation
involving one or more structural genes adjacent to the mapped location. This exploratory
proposal will identify mutations underlying the two extant mea alleles and test the
molecular sequelae of mea mutation on anterior compartment identity and development
using cutting-edge genomic tools. The mea locus has been studied for nearly 50 years,
but molecular identification eluded efforts with earlier technology. We will resolve this
genetic puzzle using de novo long read sequencing, layered onto previously unpublished
mapping data. We propose that mea mutations are regulatory in nature and affect
compartmentation or compartment-specific identity with respect in the anterior cerebellar
lobe. This predicts either discrete or graded changes in expression signatures within or
across compartments. We will test this family of hypotheses using single nucleus
sequencing of RNA and transposon-accessible chromatin sites from mutant and control
littermates in a highly congenic background. Together these aims will resolve a
longstanding mystery in the genetics of cerebellum development and point to plausible
mechanisms for pleiotropic effects on vertebral development.

## Key facts

- **NIH application ID:** 10889474
- **Project number:** 1R21NS132300-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** BRUCE A HAMILTON
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $197,500
- **Award type:** 1
- **Project period:** 2024-04-16 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10889474

## Citation

> US National Institutes of Health, RePORTER application 10889474, Meander tail and development of the anterior lobe. (1R21NS132300-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10889474. Licensed CC0.

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