# DETERMINATION OF CELL FATE BY POSITIONAL CUES

> **NIH NIH R01** · HARVARD MEDICAL SCHOOL · 1993 · $177,181

## Abstract

The long-term objectives of this proposal are to understand the way
in which multipotent embryonic cells detect their position with
respect to overall body pattern, and the way in which position-
specific environmental cues act on the multipotent cell to commit
it to one of its alternative developmental pathways.  These
problems will here e examined in the leech embryo, whose normal
development is comprised of an invariant sequence of cell lineages
in which certain uniquely identifiable cells choose between
alternative pathways on the basis of position.  One specific aim
is to use single cell ablations to identify the cells which
generate and the cells which receive positional cues.  A second aim
is to characterize the molecular basis of these positional cues.
Such cues may be transmitted via gap junctions, and this hypothesis
will be examined by injecting the interacting cells with antibodies
that bind to the major gap junction protein in order to block
transjunctional conductance.  To generate effective antibodies, a
gene for the leech gap junction protein is being isolated and
sequenced, and portions of the predicted polypeptide will be used
to immunize rabbits.  The role of the ionic environment on the
interaction of these embryonic cells will also be examined.  A
third aim is to identify molecular changes that occur in the
multipotent cells in associated with its commitment to one of its
alternative development pathways.  Toward this end, a leech embryo
cDNA library will be constructed and differential screening used
as a means of identifying gene transcripts that are uniquely
associated with a particular cell commitment.  The final specific
aim is to compare two segmentally homologous development pathways
where similar cell commitments seem to the governed by different
development mechanisms.  The results of this study will lend
insight into an important and poorly understood aspect of cell
biology, i.e. the detailed mechanisms by which spatial patterns of
cell differentiation arise during development, and are therefore
relevant to the goals of human medicine.

## Key facts

- **NIH application ID:** 2198314
- **Project number:** 5R01HD021735-08
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **SAM.gov UEI:** JDLVAVGYJQ21
- **Principal Investigator:** STANFORD MARTIN SHANKLAND
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $177,181
- **Award type:** 5
- **Project period:** 1986-04-01 → 1994-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2198314

## Citation

> US National Institutes of Health, RePORTER application 2198314, DETERMINATION OF CELL FATE BY POSITIONAL CUES (5R01HD021735-08). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2198314. Licensed CC0.

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