Sinusoids as drivers of liver development: more than simple chemistry

Abstract

Signals from cardiac mesoderm initiate liver development (1) and endothelial cells are required for liver morphogenesis and growth (2, 3). Studies performed in mice showed that specification and expansion of hepatoblasts from the endoderm are induced by endothelial cells at E8.25 via modulation of Wnt and Notch signaling (2). The nascent sinusoids and primitive vascular structures of the embryonic liver are lined between E9.5 and E10.5, guiding the localization of migrating hepatic cells to establish the architecture of the liver (3). At this initial phase of liver development, hepatocyte growth factor (HGF) is not essential for liver expansion (3), while in later phases – mainly after E14.5 – the lack of HGF expression results in fetal death (4). Hence, the factors driving the exponential growth of the liver between E10.5 and E14.5 are not fully understood.

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