# IONIC REGULATION IN THE ACTIVATION OF DEVELOPMENT

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 1994 · $153,710

## Abstract

Fertilization marks a critical transition in the development of an
organism.  After lying dormant for months to years, fertilization awakens
the oocyte, increasing its rate of metabolism and initiating its cell cycle
leading to further embryonic development.  How does sperm-egg contact
trigger this awakening in the egg?  Changes in intracellular ion
concentrations are early steps in this activation mechanism.  A transient
[Ca2+]i increase and permanent pHi increase accompany egg activation in
many species and treatments that activate eggs usually generate these ionic
changes.  Moreover, blocking the transient [Ca2+]i increase blocks egg
activation in all species studied, so this change is critical for the
activation of development.  The central question we are asking is how does
the sperm trigger these ion concentration changes in the vertebrate egg?
We will use the frog egg as a model system and test two main hypotheses.
One states that the sperm introduces sufficient Ca2+ into the egg to
trigger a process of Ca2+-induced Ca2+ release and the other is that the
sperm triggers a wave of phosphatidyl inositol lipid hydrolysis that
generates inositol trisphosphate (IP3) that in turn releases Ca2+ from the
ER.  We will also determine the mechanism for wave propagation in the frog
egg.  Specifically, we will determine if the wave spreads throughout the
egg and if the mechanism of spread is the same in the cortical region near
the plasma membrane as it is deep in the egg.  Next, we will determine the
mechanism of Ca2+ removal from the cytoplasm and how this might be linked
to the permanent pHi increase that begins at the same time that [Ca2+]i is
falling.

After determining how the increase in [Ca2+]i is triggered and propagated.
we will turn to pHi.  There are several hypotheses we will test, including
the possibility that the other byproduct of lipid hydrolysis,
diacylglycerol, triggers the pHi increase by stimulating protein kinase C.
Other ideas to be investigated include the possibility that the same
mechanism pumping Ca2+ out of the cytoplasm also moves protons out.
Finally, there is a good chance that the alkalinization is a byproduct of
other metabolic changes occurring at activation.

This research will clarify the relationships between the inositol lipid
cascade, pHi and [Ca2+]i in a system that naturally undergoes physiological
pHi and [Ca2+]i changes.  Such information should prove valuable for the
understanding of many cellular mechanisms which utilize pHi and/ir [Ca2+]i
as regulatory agents.

## Key facts

- **NIH application ID:** 2197919
- **Project number:** 2R01HD019966-09
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **SAM.gov UEI:** TX2DAGQPENZ5
- **Principal Investigator:** RICHARD Lee NUCCITELLI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $153,710
- **Award type:** 2
- **Project period:** 1985-04-01 → 1999-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2197919

## Citation

> US National Institutes of Health, RePORTER application 2197919, IONIC REGULATION IN THE ACTIVATION OF DEVELOPMENT (2R01HD019966-09). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2197919. Licensed CC0.

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