Sonic hedgehog signaling is required for sympathetic nervous system development

Abstract

Sonic hedgehog (Shh) plays critical roles during nervous system development, yet little is known about its function in the sympathetic nervous system. Using a mouse Shh null line, we examined the roles of Shh during SNS development. Loss of Shh did not prevent formation of the sympathetic trunk, but the ganglia are hypoplastic and misspatterned. Neuronal differentiation was delayed in Shh mutant embryos showing that Shh is required for correct developmental timing in addition to its role in sympathetic nervous system patterning. Immunohistochemical analyses of the ganglia for expression of the pan-neuronal marker beta3-tubulin, the noradrenergic biosynthetic enzyme tyrosine hydroxylase and the glial marker B-FABP showed that Shh is not required for differentiation of sympathetic neurons or glia.

Human axial progenitors generate trunk neural crest cells in vitro

“…We next sought to determine whether trunk NC cells derived from axial progenitors are the optimal source of sympathoadrenal (SA) progenitors and their derivatives. The BMP and sonic hedgehog (SHH) signalling pathways have been shown to be critical for the specification of these lineages from NC cells ( Oh et al, 2016 ; Schneider et al, 1999 ; Morikawa et al, 2009 ). Therefore we cultured d8 trunk NC cells generated from axial progenitors carrying a GFP reporter within the SA/sympathetic neuron regulator PHOX2B locus ( Oh et al, 2016 ; Pattyn et al, 2000 ), in the presence of BMP and sonic hedgehog (SHH) signalling agonists ( Figure 5A ).…”

Functional Coupling with Cardiac Muscle Promotes Maturation of hPSC-Derived Sympathetic Neurons

“…After selecting phenotypically and karyotypically normal lines (Figure 1B, 1E, and S1A–S1B), we searched for sympathetic neuronal differentiation. In animal models, specification of sympathetic neurons and chromaffin cells are specified from migrating neural crest stem cells by SHH and BMP signaling (Morikawa et al, 2009; Schneider et al, 1999). We initially induced neural crest cells using SMAD inhibition (termed ‘LSB’ for inhibitors LDN193189 and SB431542) protocol (Chambers et al, 2009).…”

“…Like migrating sympathoadrenal neural crests in developing animal embryos (Morikawa et al, 2009; Saito et al, 2012; Schneider et al, 1999), activation of SHH and BMP signaling pathways appears crucial for our sympathetic neuronal specification with hPSC-based system (Figure 1G–1J and S1C–S1D), which allows us to recapitulate human sympathetic neuron specification in vitro . Our characterization of the in vitro molecular profile and functional properties shows that they are similar to those of their in vivo counterparts, including the expression of autonomic/sympathetic marker genes, catecholaminergic enzymes, capacity for NE-release, and electrophysiological profiles, such as phasic/tonic APs and medium AHP (Figure 1L, 2E–2H, 3B–3I, 5E–5F, S2D, S3A–S3I, and S3L–S3V).…”

Human axial progenitors generate trunk neural crest cells

“…We next sought to determine whether trunk NC cells derived from axial progenitors are the optimal source of sympathoadrenal (SA) progenitors and their derivatives. The BMP and sonic hedgehog (SHH) signalling pathways have been shown to be critical for the specification of these lineages from NC cells (74, 75). Therefore we cultured d8 trunk NC cells generated from axial progenitors carrying a GFP reporter within the SA/sympathetic neuron regulator PHOX2B locus (18, 76), in the presence of BMP and sonic hedgehog (SHH) signalling agonists ( Figure 5A ).…”