# NUCLEAR DETERMINATION AND DIFFERENTIATION IN DEVELOPMENT

> **NIH NIH R01** · SYRACUSE UNIVERSITY AT SYRACUSE · 1994 · $251,402

## Abstract

During early embryogenesis cells become determined to differentiate along
specialized pathways.  The molecular events underlying these processes are
not understood.  The long-term objective of this project is to obtain an
understanding of the steps involved in nuclear determination and
differentiation.  To this end, specific attention is being paid to changes
in histone composition, histone modifications and chromatin structure in
specific nuclei undergoing divergent pathways of differentiation.
Conjugation in Tetrahymena will be used as a model to study nuclear
determination and differentiation during development.  In this system,
nuclei derived from daughter products of a single mitotic division
differentiate into distinctly different products, macro-and micronuclei
depending upon their location within the cell.  In many ways these events
are directly analogous to cellular determination and differentiation which
characterize embryogenesis of higher animals.

A variety of biochemical, cytological, immunological and micromanipulation
approaches will be used to 1) further define the histone composition,
histone modification and chromatin structure in synchronous populations of
developing nuclei isolated from conjugating cells as well as nuclei in
various stages of the cell cycle; 2) fractionate, purify and characterize
enzymes which play a role in the histone remodeling process; 3) purify,
characterize and compare the linker histones in micro- and macronuclei and
study their effects on chromatin higher order structures; 4) generate and
use antibodies to specific histones as probes in projects which include
protein purification, protein structure-function relationships, chromatin
structure and fractionation, cloning of Tetrahymena histone genes as well
as immunofluorescent analyses with conjugating cells; and 5) microinject
molecules into and micromanipulate nuclei within living cells to ask
questions concerning the targeting of histones to the proper nuclear
compartment, the consequences on histone metabolism and function by
perturbation with specific antibody molecules and the role that cytoplasm
plays in directing nuclear determination and differentiation.
Understanding these mechanisms in normal development is essential if we are
to understand cases of abnormal development, some congenital diseases and
certain pathological situations such as neoplastic transformation.

## Key facts

- **NIH application ID:** 2197283
- **Project number:** 5R01HD016259-13
- **Recipient organization:** SYRACUSE UNIVERSITY AT SYRACUSE
- **Principal Investigator:** CHARLES DAVID ALLIS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $251,402
- **Award type:** 5
- **Project period:** 1990-07-01 → 1995-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2197283

## Citation

> US National Institutes of Health, RePORTER application 2197283, NUCLEAR DETERMINATION AND DIFFERENTIATION IN DEVELOPMENT (5R01HD016259-13). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2197283. Licensed CC0.

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