Development of endodermal organs is dependent on interaction between the endoderm and the surrounding mesoderm. Endodermal tissue cultured in vitro does not differentiate without its surrounding mesoderm; endodermal tissue co-cultured in vitro with splanchnic mesoderm undergoes organ-specific differentiation. Furthermore, organ development depended on the position of the mesoderm -- not the endoderm -- along the antero-posterior axis. For example, tracheal bud endoderm cultured with mesoderm from different regins differentiates according to location from where mesoderm derived. Mesoderm fromnear liver leads to liver-like tubues in the tracheal bud. Mesoderm outside the immediate splanchnic layer also instructs the endoderm.
For example, as we will discuss in more detail below, signals from the notochord (dorsal of the endoderm) and the heart primordium (antero-ventral of the endoderm) play an essential role in the specification of the pancreas and liver, respectively. Inductive signals also pass from the endoderm to the mesoderm. In other words, signaling between the mesoderm and endoderm is reciprocal. Thus, endoderm co-cultured with somitic mesoderm (which normally forms muscle and bone) will induce the mesoderm to become smooth muscle.
Shh, TGFβ and FGF
Hedgehog, TGFβ and FGF are families of regulatory genes involved in endo-mesodermal interactions and are critical for region-specific endodermal differentiation.
|Ssh||Notochord||Hedgehog genes (Shh and Ihh) are expressed in the endoderm and are regulated by signals from the surrounding mesoderm. Ssh-/- mice have overall smaller guts, and regional abnormalities as well: stomach epithelium (specialized crypts with acid-producing cells) is replaced by intestine-like epithelium (villi containing absorptive cells). FGF and TGFβ genes repress Shh expression in the region of dorsal endoderm that gives rise to the posterior stomach, spleen and pancreas. In regions of the endoderm where Ssh is not repressed, it upreguates BMP expression in the splanchnic mesoderm.|
|TGFβ||Notochord||Loss of notochord-derived TGFβs allows ectopic posterior Ssh expression in the dorsal endoderm: the spleen and pancreas are reduced or absent.|
|FGF||Cardiac||FGF signaling from the cardiac mesoderm (aka heart) is critical for liver formation. In contrast, signals from the notochord (such as Shh) suppress liver formation. Thus, placing notochord tissue next to ventral endoderm results in absence of a liver. Liver formation is monitored via albumin, a marker of liver tissue that is expressed even before the liver bud forms.|
|BMPs are required in the splanchnic mesoderm for proliferation and differentiation as smooth muscle.|