# RETINOIDS IN VERTEBRATE DEVELOPMENT

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 1994 · $141,795

## Abstract

The research described in this application explores the role of retinoic
acid (RA) and other biologically active retinoids in vertebrate
development and is important for a proper understanding of the physiologic
role of RA in vertebrate limb morphogenesis. The dose-dependent effect of
RA on the limb digit pattern, the similarity between the effect of RA and
of the ZPA (an endogenous signaling region), the presence in the limb bud
of RA, of retinoid receptors, of RA biosynthetic enzymes and of retinoid
binding proteins, collectively lend credence to the hypothesis that RA is
or closely mimics a hypothetical morphogen released by the ZPA. However,
tissue isolated from an RA-exposed bud can induce pattern duplications,
hence RA may convert non-ZPA tissue into ZPA and not be a morphogen. To
test these two possibilities and to further examine the physiologic role
of RA in limb development, we propose the following studies: (1) We now
have evidence
that only pharmacologic but not physiologic doses of RA induce ZPA. To
pursue this important finding, we will exploit the fact that grafts of
authentic ZPA induce in the host HoxD11, 12, and 13 genes. Hence, we will
treat quail wing buds with different doses of RA, transplant the tissue
into a chick host and measure the induction of HoxD genes in the host
tissue in dependence of the dose of RA to which the graft was exposed. (2)
To determine whether the effect of two naturally occurring retinoids, RA
and 9-cis-RA is mediated either by homodimers of retinoid-X-receptors
(RXRs) or RA-receptors (RARs) or by RXR-RAR heterodimers, we will treat
wing buds with RAR- or RXR-specific synthetic retinoids. (3) In vivo
experiments have revealed local difference in retinoid metabolism along
the anterioposterior axis of the limb bud. To quantify these differences,
anterior and posterior limb bud tissue will be incubated separately in
media containing either retinol, retinal, RA, or 9-cis-RA, and the
relative rates of enzymatic conversion will be determined. This will
reveal whether or not the ZPA is a high point of RA and/or 9-cis-RA
production. (4) Retinol dehydrogenase (RDH) and retinal dehydrogenase
(RalDH) are two key enzymatic activities catalyzing RA synthesis, and are
both present in chick limb buds and embryos. Using sensitive enzymatic
assays for RDH and RalDH, we will purify both enzymes to homogeneity from
embryos. Partial protein sequence will be used to generate oligonucleotide
probes to clone the corresponding genes. To reveal where and when in the
limb bud and in the embryo RDH and RalDH are expressed and hence which
sites serve as local retinoid sources, embryos will be subjected to in
situ hybridization using RDH- and RalDH-specific probes. Although this
proposal centers on the role of retinoid in vertebrate limbs; the
resulting information will increase our general understanding of this
important class of signaling molecules in normal development as well as in
embryos exposed to high, teratogenic doses o...

## Key facts

- **NIH application ID:** 2197971
- **Project number:** 2R01HD020209-10A1
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **SAM.gov UEI:** FXKMA43NTV21
- **Principal Investigator:** GREGOR EICHELE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $141,795
- **Award type:** 2
- **Project period:** 1985-09-01 → 1999-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2197971

## Citation

> US National Institutes of Health, RePORTER application 2197971, RETINOIDS IN VERTEBRATE DEVELOPMENT (2R01HD020209-10A1). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2197971. Licensed CC0.

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