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Volume 48(5): 603-611, 2000
The Journal of Histochemistry & Cytochemistry
http://www.jhc.org
ARTICLE
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Differentiai Expression of Peroxisome Proliferator-activated
Receptors {PPARs} in the Developing Human Fetal
Digestive Tract
Cécile Huin, Lina Corriveau, Arnaud Bianchi, Jean Marie Keller, Philippe Collet,
Pascaline Krémarik-Bouillaud, Lionel Domenjoud, Philippe Bécuwe, Hervé Schohn,
Daniel Ménard, and Michel Dauça
Laboratoire de Biologie Cellulaire du Développement, EA 2402 "Proliférateurs de Peroxysomes," Faculté des Sciences,
Vandoeuvre-les-Nancy, France (CH,AB,JMK,PC,PKB,LD,PB,HS,MD), and Groupe CRM de Recherche sur le Développement
Fonctionnel et la Physiopathologie du Tube Digestif, Département Anatomie et Biologie Cellulaire, Faculté de Médecine,
Sherbrooke, Québec, Canada (LC,DM)
5 U M MARY We investigated the spatiotemporal distributions ofthe different peroxisome
proliferator-activated receptor (PPAR) isotypes (a, [3, and -y) during development (Week 7.
to Week 22 of gestation) of the human fetal digestive tract by immunohistochemistry using
specifie polyclonal antibodies. The PPAR subtypes, including PPAR-y, are expressed as early
as 7 weeks of development in cell types of endodermal and mesodermal origin. The presence
of PPAR-y was also found by Western blotting and nuclease-S 1 protection assay, confirming
that this subtype is not adipocyte-specifie. PPARa, PPAR[3, and PPAR-y exhibit different
patterns of expression during morphogenesis of the digestive tract. Whatever the stage
and thegut region (except the stomach) examined, PPAR-y is expressed at a high level, suggesting
some fundamental role for this receptor in development and/or physiology of the
human digestive tract. (J Histochem Cytochem 48:603-611, 2000)
KEY WORDS
PPARs
development
differentiation
fetus
digestive tract
PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS
(PPARs) are transcription factors belonging to the nuclear
receptor superfamily and have been initiaUy described
as ~olecular targets for compounds that cause
peroxisome proliferation (for review see S0rensen et
al. 1998). To date, three isotypes of PPAR have been
described in humans: œ (Sher et al. 1993); NUC1, also
caUed [3 or 0 (Schmidt et al. 1992); and 'Y (Elbrecht et
al. 1996; Fajas et al. 1997). There are three subtypes
of PPAR"I mRNA, transcribed from three different
promoters, which give rise to two proteins, ppAR"11
and "12, as the protein encoded by PPAR"I3 mRNA is
indistinguishable from PPAR"Il (Fajas et al. 1998).
In humans, PPARœ is present mainly in liver, heart,
and kidney, whose tissues exhibit high fatty acid metab-
Correspondence to: C. Huin, Laboratoire de Biologie cellulaire
du Développement, UPRES 2402 "Proliférateurs de Peroxysomes,"
Faculté des Sciences, BP 239, 54506 Vandoeuvre-les-Nancy Cedex,
France.
Received for publication August 9, 1999; accepted ]anuary 5,
2000 (9A5061).
olism and high peroxisome-dependent activity. PPAR[3
is ubiquitously expressed in aU tissues tested, whereas
ppAR'Y predominates in adipose tissue, large intestine,
and macrophages and monocytes (Mukherjee et al.
1994; Auboeuf et al. 1997; Marx et al. 1998; Ricote et
al. 1998; Spiegelman 1998). Consistent with their 10­
calization, the PPAR subtypes play different roles. After
binding to specifie elements (PPREs), PPARœ regulates
the transcription of several target genes involved
in lipid metabolism and homeostasis (Desvergne and
Wahli 1995; Wahli et al. 1995; Lemberger et al. 1996;
S0fensen et al. 1998). PPAR"I controls adipocyte (Chawla
et al. 1994; Tontonoz et al. 1995; Schoonjans et al.
1996; Spiegelman et al. 1997) and monocyte/macrophage
(Marx et al. 1998; Ricote et al. 1998; Tontonoz et
al. 1998) differentiation. Until now, the precise role of
ppAR[3 has not yet been elucidated.
Detailed descriptions of the morphological and
functional changes occurring during the development of
the human gastrointestinal tract are available (Ménard
and Calvert 1991; Ménard 1994,1995; Montgomery
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