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The role of the Hedgehog pathway in embryonic development

Hedgehog signaling regulates cell differentiation and organ formation during embryonic development in animals.¹² It functions by time- and position-dependent expression patterns to ensure that developing tissues attain their correct size, location, and cellular content.^8,13,14 Learn more about the role of Hedgehog signaling in the development of specific embryonic tissues and organs by reading on.

Skin

The skin is responsible for forming a variety of epidermal structures that differ among vertebrates, such as feathers in birds and hair in mammals. In each instance, the specific epidermal structure arises in an area of thickening in the embryonic epithelial layer, and its function is dictated by developmental signals in that region, such as those from Hedgehog ligands.¹⁵ During the development of a normal hair follicle, Sonic Hedgehog is expressed in the thickening embryonic epithelial layer, and its receptor Patched (PTCH) is expressed in the underlying dermal layer. The binding of Sonic Hedgehog to PTCH leads to epidermal proliferation and invagination to form a hair follicle.^15,16

Cerebellum

Granule cells are tiny neurons that are the most abundant cell type in the cerebellum.¹⁷ Granule cells regulate the activity of Purkinje cells, which are large neurons responsible for motor coordination output in the cerebellum cortex.¹⁷ During normal development, a large pool of granule neuron precursors (GNPs) is generated on the surface of the developing cerebellum. PTCH restrains proliferation of GNPs until Sonic Hedgehog is secreted by Purkinje neurons. The binding of Sonic Hedgehog to PTCH relieves the repression of target gene activation and results in the proliferation of GNPs.^17-19

Pancreas

Downregulation of Hedgehog expression is required to initiate mammalian pancreatic development.²⁰ However, after the pancreas has fully developed, Hedgehog signaling appears to have a different function. Indian Hedgehog and Desert Hedgehog are expressed in adult pancreatic β-cells and appear to be involved in the regulation of insulin expression.²¹

Gut

The gastrointestinal tract develops from the embryonic gut tube, which is composed of 2 different germ layers: endoderm, which differentiates into the epithelial lining, and mesoderm.²² Folding the primitive tube into the complex adult organ depends on Hedgehog signaling between these 2 germ layers.^23,24

Lung

The mammalian lung develops by branching morphogenesis of cells of epithelial origin. Sonic Hedgehog is highly expressed in the epithelium of the lung and is thought to play a role in ensuring proper branching.²⁵