# EMBRYONIC CELL SIGNALING SPECIFICATION AND COMMITMENT

> **NIH NIH P01** · UNIVERSITY OF OREGON · 1994 · $1,217,747

## Abstract

We will continue our Program Project to learn the mechanisms of cell
signaling, specification and commitment during embryonic development.  We
propose three component projects, each addressing
one of these three issues.  We will carry out these studies in the
zebrafish, Brachydanio rerio, because of the advantages it offers as an
experimental system, including labeling and transplanting single cells,
genetic analysis of developmental pathways, and production of transgenic
animals.   Specifically, we propose to examine induction of the nervous
system and the development of two cell lineages -- primary neurons that
form the earliest neural circuitry in the embryo and neural crest cells
that form the peripheral nervous system and structures in the head and
heart.  Induction of these lineages involves cell signaling by inducing
(growth/survival) factors, and their receptors, and depends on cell
position in the embryo.  Before overt differentiation, cells become
specified. While these specifications may involve phenotypic changes,
they do not represent irreversible commitments that restrict the cells to
a single developmental course.  We propose to examine whether these
"conditional" specifications are temporally separable from commitment in
neuronal and neural crest lineages.

Our main long-term objectives are to identify the regulatory molecules
and their genes that  underlie signaling, specification and commitment
during vertebrate development, and to discover their functional
interactions.  Disruption of such mechanisms during development of the
human central and peripheral nervous systems results in numerous diseases
or syndromes, including (a) hereditary dysplasias and neuropathies such
as Familial Dysautonomia, Hirschprung's disease (aganglionic megacolon),
and orthostatic hypotension; (b) hereditary metaplasias, such as von
Recklinghausen's disease (Neurofibromatosis); (c) numerous neoplasias,
such as gliomas, neuroblastomas, and pheochromocytomas; and (d)
congenital defects such as spina bifida, cleft lip/palate, and
craniofacial defects associated with heart malformation (e.g. Pierre
Robin syndrome).  A detailed understanding of the regulatory mechanisms
of normal neural development in vertebrates embryos will help elucidate
such disease processes.

## Key facts

- **NIH application ID:** 2198542
- **Project number:** 5P01HD022486-08
- **Recipient organization:** UNIVERSITY OF OREGON
- **SAM.gov UEI:** Z3FGN9MF92U2
- **Principal Investigator:** JAMES A WESTON
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $1,217,747
- **Award type:** 5
- **Project period:** 1987-02-01 → 1997-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2198542

## Citation

> US National Institutes of Health, RePORTER application 2198542, EMBRYONIC CELL SIGNALING SPECIFICATION AND COMMITMENT (5P01HD022486-08). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2198542. Licensed CC0.

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