INTRODUCTION
Fatty acid binding proteins (FABPs) constitute a multigene
family of small intracellular proteins that bind hydrophobic
ligands such as fatty acids, eicosanoids and retinoids. More
than 12 different FABPs have been described (Börchers and
Spener, 1994) and by sequence homology they can be classi-
fied into 4 major subfamilies: heart-, liver- and intestinal type
FABPs as well as the group of cellular retinoid binding
proteins (CRtBPs).
FABPs, in general, are synthesised in specific differentiated
tissues (Matarese et al., 1989; Veerkamp et al., 1991). The
physiological roles of FABPs remain imperfectly understood
while structural diversity, tissue and ligand specificity suggest
distinct functional specializations (Kaikaus et al., 1990).
Evidence supports a dual function: alleviation of intracellular
transport and metabolism of their hydrophobic ligands and
sequestration of ligands in a manner that limits their associa-
tion with alternative binding sites, in particular with members
of the nuclear hormone receptor superfamily such as the
retinoic acid receptors (RAR, RXR), and the peroxisome pro-
liferator activated receptors (PPAR). In the case of CRtBPs,
evidence has been provided that the binding protein-ligand
complexes act as direct substrates in several steps of retinoid
conversion (Napoli, 1993; Posch et al., 1992). Thereby, these
proteins may be implicated in the generation of retinoic acid
gradients. It was suggested that other FABPs might fulfill a
similar role with respect to hydrophobic ligands, such as fatty
acids or their metabolites, for other members of the large
nuclear hormone receptor family such as PPAR or one of the
‘orphan’ receptors (Bass, 1993; Issemann et al., 1992). This
hypothesis is based on observations that expression of liver-
and adipocyte-FABP is induced by fatty acids in hepatocytes
and adipocytes (Kaikaus et al., 1993; Grimaldi et al., 1992),
respectively, that PPAR induces FABP expression in hepato-
cytes (Brandes et al., 1990), that overexpression of liver-FABP
in hepatoma cells increased their growth response to linoleic
acid (Keler and Sorof, 1993), and that fatty acids and
eicosanoids may activate PPAR and RXR (Eager et al., 1992;
Keller et al., 1993).
We have been studying the function of mammary derived
growth inhibitor (MDGI) (Böhmer et al., 1987), which is
2637
Development 120, 2637-2649 (1994)
Printed in Great Britain © The Company of Biologists Limited 1994
Fatty acid binding proteins (FABPs) are a multigene family
of small intracellular proteins that bind hydrophobic
ligands. In this report we describe the cloning and
expression pattern of a novel member of this gene family
that is specifically expressed in the developing and adult
nervous system and thus was designated brain (B)-FABP.
B-FABP is closely related to heart (H)-FABP with 67%
amino acid identity. B-FABP expression was first detected
at mouse embryonic day 10 in neuroepithelial cells and its
pattern correlates with early neuronal differentiation.
Upon further development, B-FABP was confined to radial
glial cells and immature astrocytes. B-FABP mRNA and
protein were found in glial cells of the peripheral nervous
system such as satellite cells of spinal and cranial ganglia
and ensheathing cells of the olfactory nerve layer from as
early as embryonic day 11 until adulthood. In the adult
mouse brain, B-FABP was found in the glia limitans, in
radial glial cells of the hippocampal dentate gyrus and
Bergman glial cells. These findings suggest a function of B-
FABP during neurogenesis or neuronal migration in the
developing nervous system. The partially overlapping
expression pattern with that of cellular retinoid binding
proteins suggests that B-FABP is involved in the metabo-
lism of a so far unknown hydrophobic ligand with potential
morphogenic activity during CNS development.
Key words: fatty acid binding protein, gene isolation, radial glia,
ensheathing cells, satellite cells, neuroepithelium, CNS development,
mouse
SUMMARY
The expression pattern of a novel gene encoding brain-fatty acid binding
protein correlates with neuronal and glial cell development
Andreas Kurtz
1
, Andreas Zimmer
1
, Frank Schnütgen
2
, Gerold Brüning
3
, Friedrich Spener
2
and
Thomas Müller
4,
*
1
Unit on Developmental Biology, National Institute of Mental Health, Bethesda, USA
2
Department of Biochemistry, University of Münster, Germany
3
Department of Anatomy, Free University of Berlin, Berlin, Germany
4
Max-Delbrück-Center for Molecular Medicine, Berlin, Germany
*Author for correspondence at his present address: Laboratory of Molecular Biology, NINDS, Bldg. 36, Room 3D02, National Institutes of Health, Bethesda, MD 20892,
USA