Developmental expression of the homeobox protein Distal-less 3 and its relationship to progesterone production in mouse placenta

Abstract

Distal-less 3 (Dlx3) is a homeobox factor that functions as a placental-specific transcriptional regulator. Dlx3 null mice ( / ) have compromised placental development and do not survive in utero past embryonic day (E) 9·5. The current studies were undertaken to examine the expression of Dlx3 in mouse placenta during gestation, and to determine whether Dlx3 was involved in placental progesterone production. Dlx3 was not detectable at E8·5 but was detected in E9·5 placenta with continuing but diminished expression through E15·5. Dlx3 immunolocalization was restricted to the labyrinth, was nuclear and was found in cytokeratin-positive cells. Previous studies in choriocarcinoma cell lines support the conclusion that Dlx3 is required for expression of 3 -hydroxysteroid dehydrogenase VI (3 HSD VI), an obligate enzyme in the production of progesterone by trophoblast giant cells. In a rat trophoblast stem cell line (Rcho-1), Dlx3 expression was non-detectable in Rcho-1 cells induced to differentiate using mitogen withdrawal. In vitro progesterone production in placental cultures and 3 HSD VI mRNA from Dlx3 (+/+), (+/ ) and ( / ) mice were equivalent. In situ hybridization for 3 HSD VI revealed mRNA expression restricted to trophoblast giants cells with no detectable expression in the labyrinth suggesting that Dlx3 and 3 HSD VI were not colocalized within the placenta. These studies support the conclusion that Dlx3 protein expression is restricted to the labyrinth region of the murine placenta into late gestation and that Dlx3 does not appear to be expressed in trophoblast giant cells. Further, loss of Dlx3 was not correlated with synthesis of progesterone from E9·5 mouse placentas.

Early patterning of the chorion leads to the trilaminar trophoblast cell structure in the placental labyrinth

“…The expression of several genes has been shown to be localized to the labyrinth including Gcm1 Basyuk et al, 1999), Dlx3 (Berghorn et al, 2005;Morasso et al, 1999), Nr6a1 (Morasso et al, 1999;Schreiber et al, 2000;Susens et al, 1997), Tead3 (Anson-Cartwright et al, 2000Jacquemin et al, 1998), Tcfeb (Steingrimsson et al, 1998;Tompers et al, 2005;Voss et al, 2000), Esx1 (Li et al, 1997;Morasso et al, 1999;Voss et al, 2000), Hand1 (Scott et al, 2000;Simmons et al, 2007) and Syna and Synb (Dupressoir et al, 2005). Of these genes, some show layerspecific expression that has allowed insight into the early developmental origins of the three cell types (see summary in Fig.…”

DLX3 c.561_562delCT mutation causes attenuated phenotype of tricho‐dento‐osseous syndrome

“…The distal-less 3 homeobox gene, DLX3, is located on chromosome 17q21 and has diverse temporal expression in epithelial and mesenchymal tissues [Robinson and Mahon, 1994;Weiss et al, 1994;Berghorn et al, 2005]. Mutations in DLX3 (NM_ 005220.2) cause autosomal dominant trichodento-osseous (TDO) syndrome (OMIM # 190320) comprising marked changes in the hair, teeth, and bone [Lichenstein et al, 1972;Wright et al, 1997;Price et al, 1998a].…”

A 4 bp deletion mutation in DLX3 enhances osteoblastic differentiation and bone formation in vitro

“…Placental failure in mice lacking the homeobox DLX3 gene results in embryonic death between E 9.5 and E 10 due to placental defects that prevent normal development of the labyrinthine layer, possibly due to an abnormality in placental growth factor (PGF) expression. [6][7][8] DLX genes play important roles in skeletal patterning, and expression of DLX3 in the mouse embryo is associated with new bone formation and regulation of osteoblast differentiation. [9][10][11][12] DLX3 is expressed in osteoblasts, and over-expression of DLX3 in osteoprogenitor cells promotes the induction of osteoblastic differentiation markers such as type 1 collagen, bone sialoprotein, osteocalcin, and alkaline phosphatase.…”