Endoderm Development and Gut Tube Formation

Endoderm Development

• Endoderm arises from two sources: primitive and definitive endoderm.
• Primitive endoderm forms the yolk sac and assists in gastrulation.
• Definitive endoderm enters the primitive streak during gastrulation, integrating with the primitive endoderm layer.
• Sox17 is a transcription factor marking endoderm cells as they leave the primitive streak.
• Sox17 is essential for definitive endoderm formation.
• High Nodal signaling induces Sox17 (endoderm fate), while BMPs and FGFs specify mesoderm by opposing Nodal.
• Anterior-posterior axis specification involves varying Wnt/FGF/BMP levels.
• Low Wnt/FGF/BMP levels (anterior) guide lung and thyroid precursor development.
• Moderate Wnt/FGF/BMP levels (central) guide liver and pancreas precursors.
• High Wnt/FGF/BMP levels (posterior) guide intestinal progenitors.

Gut Tube Formation

• Gut cells initially form a flat sheet beneath/around the embryo.
• Tube formation occurs at anterior intestinal portal (AIP) and caudal intestinal portal (CIP).
• Unique junctions form where endoderm meets ectoderm at the oral (anterior) and anorectal (posterior) junctions.
• Oral opening forms at ~22 days.
• Rathke's pouch (anterior pituitary) originates from oral ectoderm.
• Infundibulum (posterior pituitary) originates from diencephalon neural tissue.
• Sox17 marks the boundary between ectoderm and endoderm in the mouth, including teeth and major salivary glands.
• Posterior taste buds and posterior glands are endodermal in origin.

Regional Specification of Gut Endoderm

• Wnt signals from the posterior mesoderm (guided by RA and FGF) activate transcription factors Cdx1 and Cdx2.
• High Cdx levels lead to large intestine development, low levels to small intestine.
• Cdx2 inhibits genes (like Hhex) that block stomach, liver, and pancreas development in posterior regions.
• Wnt inhibition allows these organ formations in the anterior region.
• Barx1 activates Wnt antagonists (sFRP1 and sFRP2), blocking Wnt signaling and allowing stomach development.
• Shh from endoderm induces Hox genes in mesoderm, crucial for precise regional gut specification.

Muscular Layer Formation

• Sequential muscle layer formation: inner circumferential layer and outer longitudinal layer.
• Signal regulation of muscle pattern: Shh induces BMP, restricting initial muscle formation to the inner layer.
• BMP antagonists from the inner layer and enteric neurons facilitate outer layer muscle formation.
• Mechanical forces and muscle alignment: continuous tension aligns inner layer cells circumferentially.
• Cyclic contractions align outer layer cells longitudinally.
• Villi and ISCs development: Mesoderm compression shapes villi, and Shh and BMP signaling limit intestinal stem cell formation to villi bases.

Pancreas Development

• Pancreas initially develops with two buds (dorsal and ventral).
• Ventral pancreas migrates and fuses with dorsal pancreas to form one pancreas in most humans.
• One duct remains that enters the duodenum.

Liver Development

• Ectoderm and notochord inhibit liver-specific gene expression in endoderm.
• Cardiogenic mesoderm releases FGFs, adjacent mesenchyme secretes BMPs that activate liver-specific genes.
• FGFs and BMPs promote liver development while suppressing pancreatic gene expression.

Pdx1 Gene Expression Induction

• Blood vessels induce Pdx1 expression, triggering pancreatic bud development from the endodermal tube.
• Blood vessels are crucial for Pdx1 expression and pancreatic development.
• Islets of Langerhans secrete insulin (beta cells).
• Islets secrete VEGF to attract blood vessels for islet surrounding.

Pancreatic and Liver Cell Lineages

• All pancreatic cells express Pdx1, differentiating them from liver-forming cells.
• Ngn3 expressing cells lead to endocrine progenitors (hormone production).
• Ptf1a-expressing cells form exocrine progenitors (digestive enzymes).
• Endocrine progenitors form beta, delta, and PP cells.

Cell Therapy

• Developmental biology aims to replace damaged cells with functional ones, such as insulin-secreting pancreatic beta cells.
• Induced pluripotent stem cells (iPSCs) can be reprogrammed from adult cells to resemble embryonic stem cells.
• iPSCs can effectively differentiate into pancreatic beta cells and cure diabetes in animal models.

Foregut Partitioning

• Foregut partitions into the esophagus and respiratory diverticulum during the third and fourth weeks of gestation.
• Wnt from mesenchyme determines whether the esophagus or respiratory tube develops.
• Wnt signaling determines trachea or lung formation.

Branching Morphogenesis

• Branching continues to form the lung structure.
• Branching is stereotypical and follows a well-defined lineage map.
• Branching patterns include planar bifurcation, orthogonal bifurcation, and domain branching in the bronchial epithelium.

Smooth Muscle in Lung Branching

• Mammals and birds have distinct developmental approaches to lung branching.
• Smooth muscle differentiation at branch tips initiates cleft formation connecting with proximal branch smooth muscle.
• Smooth muscle contraction at the branch tip promotes bifurcation.
• Bifurcation disruption prevents terminal branching.
• Smooth muscle differentiation aligns with epithelial markers (E-cadherin).

Mouse and Avian Lung Branching

• Both mice and birds have branched airways.
• Mice use smooth muscle contraction to create bifurcations of lung buds.
• Birds use apical constrictions to initiate new branch points.
• Both require FGF signaling from mesenchyme to promote branching.

Explore the crucial processes involved in endoderm development and gut tube formation. This quiz covers the roles of primitive and definitive endoderm, transcription factors like Sox17, and the specification of gut precursors along the anterior-posterior axis. Test your understanding of these essential biological mechanisms.