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Endodermally derived organs of the gastrointestinal and respiratory system form at distinct anterioposterior and dorsoventral locations along the vertebrate body axis. This stereotyped program of organ formation depends on the correct patterning of the endodermal epithelium so that organ differentiation and morphogenesis occur at appropriate positions along the gut tube. Whereas some initial patterning of the endoderm is known to occur early, during germ-layer formation and gastrulation, later signaling events, originating from a number of adjacent tissue layers, are essential for the development of endodermal organs. Previous studies have shown that signals arising from the notochord are important for patterning of the ectodermally derived floor plate of the neural tube and the mesodermally derived somites. This review will discuss recent evidence indicating that signals arising from the notochord also play a role in regulating endoderm development.
FIG. 1. Juxtaposition of the notochord and dorsal endoderm tissues in mouse, chick, and frog embryos. In all cases, the notochord (arrow)
contacts the dorsal endoderm (arrowheads). The positions of the neural tube (nt) and somites (s) are indicated. (A) Transverse section
through the foregut of a stage 34 frog embryo. (B) Transverse section through the hindgut of a HH stage 12 chick embryo. (C) Transverse
section through the foregut of an E8.5 mouse embryo. (D) Diagram showing dorsolateral signaling from the notochord to the neural tube
and somites (red) and ventral signaling to the endoderm (yellow). Note the marked difference in the size of the notochord relative to
surrounding tissues in these three organisms.
FIG. 2. Schematic diagram of notochord signaling to dorsal pancreatic
endoderm. Red indicates SHH expression, blue indicates
pdx1 expression, and yellow indicates pancreatic markers. (A)
Signals from the notochord cause repression of SHH expression
(red) in the pancreatic endoderm and expression of pancreatic
genes, such as pdx-1 (blue). (B) The pancreatic buds develop on
dorsal and ventral portions of the gut tube, surrounded by mesenchyme
(indicated by squiggly lines). Both pancreatic buds express a
range of pancreatic markers (yellow). (C) When the notochord is
removed, the dorsal bud evaginates, but does not undergo further
branching and morphogenesis. In addition, SHH expression is
initiated in the dorsal pancreatic epithelium and pancreatic markers
are repressed. The ventral bud develops unhindered.
FIG. 3. Notochord signals influence development of the amphibian hypochord. VEGF expression, detected by in situ hybridization, is used as
a marker for the hypochord. (A) Transverse section through the midgut region of a stage 32 frog embryo. The hypochord develops from the dorsal
endoderm, immediately ventral to the notochord. The hypochord (h) is indicated. (B) Removal of the notochord at stage 14 results in the failure
of hypochord formation. Somitesfuse medially, separating the neural tube and the endoderm. Dorsal endoderm (de) and the normal position of
the hypochord (arrowhead) are indicated. (C) Transplantation of an additional notochord results in the development of an enlarged hypochord.
The endogenous notochord is on the left and the transplanted notochord on the right. Notochord (n) and somites (s) are indicated.