Table 1.
Mechanisms and functions of canonical and non-canonical Hedgehog (Hh) signaling in neural development.
| Canonical | Non-Canonical | |||||
|---|---|---|---|---|---|---|
| Neural Cell Proliferation | Neural Progenitor Specification | Axon Guidance | Neuronal Differentiation | Axon Guidance | Axon Guidance | |
| Receptors | Ptch, Smo (Gas1, Boc) | Ptch, Smo | Ptch, Smo | Ptch, Smo | Smo, Boc | (1) Smo (mouse), Hhip (chick) (2) Boc (3) Smo, Gas1 |
| Second messengers | IP3, Ca2+ | (1) 14-4-3, cAMP (3) Gnaz |
||||
| Transcription factors | Gli | Gli | Gli | cJun | Transcription independent | Transcription independent |
| Targets | Bcl2, P53, cyclin A, B, E, D1 | Nkx2.2, Nkx6.1, Pax6, Evx1, Phox2A, Gata2, Fox2A, etc. | (1) Slit (2) Stromal cell-derived factor 1 |
Tlx3 | Src | |
| Subcellular needs for Hh signaling | Nucleus Primary cilium? |
Nucleus Primary cilium |
Nucleus | Nucleus Primary cilium? |
Axonal growth cone | Axonal growth cone |
| Main roles | Regulation of cell cycle progression and cell survival | Spinal cord and brain patterning during morphogenesis | (1) Midline crossing forebrain commissural axons (2) Retinal ganglion cell axon guidance |
Specification of spinal neuron transmitter phenotype | Attractant guidance commissural spinal axons | (1) Repulsive guidance commissural spinal axons (2) Repulsive retinal ganglion cell axon guidance (3) Repulsive guidance enteric axons |
?: Not yet determined or neural structure dependent. Bcl2: B-cell lymphoma 2; Boc: brother of cell adhesion molecule-related/down-regulated by oncogenes; cAMP: cyclic adenosine monophosphate; Evx1: even-skipped homeobox 1; Fox2A: forkhead box protein A2; Gas1: growth arrest specific 1; Gnaz: G Protein Subunit α Z; Hhip: hedgehog interacting protein; IP3: inositol 1,4,5-trisphosphate receptor type 3; Pax6: paired box 6; Phox2A: paired like homeobox 2A; Ptch: Patched; Smo: Smoothened; Src: proto-oncogene tyrosine-protein kinase; Tlx3: T-cell leukemia homeobox 3.