Nuclear receptor NR5A2 is required for proper primitive streak morphogenesis

• Published in: Developmental dynamics Vol. 235; no. 12; pp. 3359 - 3369
• Main Authors: Labelle‐Dumais, Cassandre, Jacob‐Wagner, Mariève, Paré, Jean‐Francois, Bélanger, Luc, Dufort, Daniel
• Format: Journal Article
• Language: English
• Published: New York Wiley‐Liss, Inc 01.12.2006
• Subjects: Animals; Base Sequence; Body Patterning - genetics; Body Patterning - physiology; Chimera - genetics; DNA Primers - genetics; Embryonic Development - genetics; Embryonic Development - physiology; Endoderm - cytology; Endoderm - metabolism; Female; Gastrula - cytology; Gastrula - metabolism; gastrulation; GATA4 Transcription Factor - genetics; Gene Expression Regulation, Developmental; Genetic Markers; Hepatocyte Nuclear Factor 4 - genetics; Male; mesoderm; Mesoderm - cytology; Mesoderm - metabolism; Mice; Mice, Knockout; NR5A2; nuclear receptor; Phenotype; Polyploidy; Pregnancy; primitive streak; Receptors, Cytoplasmic and Nuclear - deficiency; Receptors, Cytoplasmic and Nuclear - genetics; Receptors, Cytoplasmic and Nuclear - metabolism; visceral endoderm
• ISSN: 1058-8388; 1097-0177
• DOI: 10.1002/dvdy.20996

NR5A2, also known as liver receptor homologue 1 (LRH‐1) and fetoprotein transcription factor (FTF), is an orphan nuclear receptor involved in the regulation of cholesterol metabolism and steroidogenesis in the adult. NR5A2 was also shown to be expressed during early mouse embryogenesis. Consistent with its early expression pattern, a targeted disruption of this gene leads to embryonic lethality around the gastrulation period. To characterize the embryonic phenotype resulting from NR5A2 loss of function, we undertook morphological and marker gene analyses and showed that NR5A2−/− embryos display growth retardation, epiblast disorganization, a mild embryonic–extraembryonic constriction, as well as abnormal thickening of the proximo‐posterior epiblast. We demonstrated that, although initial specification of the anterior–posterior axis occurred in the absence of NR5A2, primitive streak formation was impaired and neither embryonic nor extraembryonic mesoderm was generated. Moreover, although the visceral endoderm does not show major morphological abnormalities in NR5A2−/− embryos, a decrease in the expression level of HNF4 and GATA4 was observed. Aggregation experiments demonstrated that, in the presence of wild‐type tetraploid cells, NR5A2 mutant cells in the epiblast are capable of undergoing normal gastrulation. Therefore, our results suggest a requirement for NR5A2 in extraembryonic tissues and identify a novel role of this gene in proper primitive streak morphogenesis. Developmental Dynamics 235:3359–3369, 2006. © 2006 Wiley‐Liss, Inc.