Both apolipoprotein E and A-I genes are present in a nonmammalian vertebrate and are highly expressed during embryonic development

Both apolipoprotein E and A-I genes are present in a nonmammalian vertebrate and are highly expressed during embryonic development

^*Unité de Recherche Associée 2227 du Centre National de la Recherche Scientifique, Université Paris-Sud, Bât. 447, 91405 Orsay Cedex, France; ^‡Institut de Génétique et de Biologie Moléculaire et Cellulaire, BP 163, 67404 Illkirch, Cedex, France; and ^§Loeb Institute for Medical Research, Ottawa Civic Hospital, Ottawa, Ontario, Canada K1Y 4E9

Abstract

Apolipoprotein E (apoE) is associated with several classes of plasma lipoproteins and mediates uptake of lipoproteins through its ability to interact with specific cell surface receptors. Besides its role in cardiovascular diseases, accumulating evidence has suggested that apoE could play a role in neurodegenerative diseases, such as Alzheimer disease. In vertebrates, apoA-I is the major protein of high-density lipoprotein. ApoA-I may play an important role in regulating the cholesterol content of peripheral tissues through the reverse cholesterol transport pathway. We have isolated cDNA clones that code for apoE and apoA-I from a zebrafish embryo library. Analysis of the deduced amino acid sequences showed the presence of a region enriched in basic amino acids in zebrafish apoE similar to the lipoprotein receptor-binding region of human apoE. We demonstrated by whole-mount in situ hybridization that apoE and apoA-I genes are highly expressed in the yolk syncytial layer, an extraembryonic structure implicated in embryonic and larval nutrition. ApoE transcripts were also observed in the deep cell layer during blastula stage, in numerous ectodermal derivatives after gastrulation, and after 3 days of development in a limited number of cells both in brain and in the eyes. Our data indicate that apoE can be found in a nonmammalian vertebrate and that the duplication events, from which apoE and apoA-I genes arose, occurred before the divergence of the tetrapod and teleost ancestors. Zebrafish can be used as a simple and useful model for studying the role of apolipoproteins in embryonic and larval nutrition and of apoE in brain morphogenesis and regeneration.

Footnotes

↵ † To whom reprint requests should be addressed. e-mail: Patrick.Babin{at}ibaic.u-psud.fr.
Richard J. Havel, University of California School of Medicine, San Francisco, CA
Data deposition: The sequences reported in this paper have been deposited in the GenBank database [accession nos. Y13652 and Y13653 (Danio rerio apoE and apoA-I cDNAs, respectively)].
ABBREVIATIONS:

apo,

apolipoprotein;

YSL,

yolk syncytial layer