| First Author | Hayhurst GP | Year | 2008 |
| Journal | J Hepatol | Volume | 49 |
| Issue | 3 | Pages | 384-95 |
| PubMed ID | 18617288 | Mgi Jnum | J:138863 |
| Mgi Id | MGI:3806735 | Doi | 10.1016/j.jhep.2008.04.024 |
| Citation | Hayhurst GP, et al. (2008) Morphogenetic competence of HNF4alpha-deficient mouse hepatic cells. J Hepatol 49(3):384-95 |
| abstractText | BACKGROUND/AIMS: To specify roles of HNF4alpha in mouse liver development, we have analyzed the ex vivo morphogenetic potential of HNF4alpha-null embryonic hepatic cells. METHODS: Using mice with floxed or deficiency alleles of HNF4alpha, hepatic cells lacking this transcription factor were explanted into primary culture and derived into cell lines. RESULTS: Contrary to behavior in vivo where HNF4alpha-null liver cells fail to show normal polarity and epithelialization, e18.5 hepatic cells in primary culture from mutant embryos show restoration of apical expression of tight junction protein-1 and of transcripts for E-cadherin. Clones of control and HNF4alpha-null cell lines were indistinguishable, even when differentiation of bile canalicular formation was induced. HNF4alpha-null and control cell lines showed similar potential to colonize livers of the murine ALB-uPA/SCID model of liver regeneration, but null cells formed only bile ducts and not clusters of hepatocytes. Finally, analysis of mutant embryonic livers revealed a transcriptional signature consistent with a stress response, which could underlie the morphogenetic defects observed in vivo. CONCLUSIONS: We conclude that the lack of epithelialization characteristic of the HNF4alpha-null embryonic liver is due, at least in part, to non-cell autonomous defects, and that null cells do not suffer intrinsic defects in polarization. |
