Requirement of 19K form of Sonic hedgehog for induction of distinct ventral cell types in CNS explants

Abstract

The identity and patterning of ventral cell types in the vertebrate central nervous system depends on cell interactions. For example, induction of a specialized population of ventral midline cells, the floor plate, appears to require contact-mediated signalling by the underlying notochord, whereas diffusible signals from the notochord and floor plate can induce ventrolaterally positioned motor neurons. Sonic hedgehog (Shh), a vertebrate hedgehog-family member, is processed to generate two peptides (M(r) 19K and 26/27K) which are secreted by both of these organizing centres. Moreover, experiments in a variety of vertebrate embryos, and in neural explants in vitro, indicate that Shh can mediate floor-plate induction. Here we have applied recombinant Shh peptides to neural explants in serum-free conditions. High concentrations of Shh bound to a matrix induce floor plate and motor neurons, and addition of Shh to the medium leads to dose-dependent induction of motor neurons. All inducing activity resides in a highly conserved amino-terminal peptide (M(r) 19K). Moreover, antibodies that specifically recognize this peptide block induction of motor neurons by the notochord. We propose that Shh acts as a morphogen to induce distinct ventral cell types in the vertebrate central nervous system.

21st Century neontology and the comparative development of the vertebrate skull

“…In the developing craniofacial primordia, Shh is generally restricted to epithelial layersoften in sites of epithelial-epithelial contacts (Echelard et al, 1993;Jeong et al, 2004). Both gain-and loss-offunction studies suggest that Shh has organizing potential, in particular in the axial mesendoderm (i.e., the notochord and prechordal plate; Echelard et al, 1993;Riddle et al, 1993; Johnson et al, 1994a-c; Marti et al, 1995;Chiang and Flanagan, 1996). Targeted disruption of Shh has devastating effects on cranial development: severe cyclopic holoprosencephaly (i.e., loss of midline structures) and, despite early (ϳE9.5) BA development, a near complete loss of the BA-derived structures (Chiang and Flanagan, 1996).…”

Sonic hedgehog signaling pathway in vertebrate epithelial appendage morphogenesis: perspectives in development and evolution

“…3B, [13,18]). As demonstrated in the zone of polarizing activity (ZPA) of the limb bud [2; Capdevila and Johnson, this issue] and in the spinal cord, by the floor plate which can specify ventral fate ( [57][58][59]; Patten and Placzek, this issue), SHH also functions in establishing polarizing activity. In the feather and hair, Shh becomes restrictively located to the distal and posterior ends of the buds, and may be involved in initiating anteriorposterior asymmetry.…”

Cyclops‐independent floor plate differentiation in zebrafish embryos

“…Notochord induces floor plate in amniote embryos when combined with neural tissue (van Straaten et al, 1988;Placzek et al, 1990), suggesting an instructive role of notochord in floor plate development. The secreted signalling molecule Sonic hedgehog (Shh), which is expressed in the notochord and the floor plate (Echelard et al, 1993;Krauss et al, 1993;Riddle et al, 1993;Roelink et al, 1994), induces floor plate in explants of neural tissue (Marti et al, 1995a;Roelink et al, 1995). Moreover, when Shh is inactivated through the use of antibodies in the chicken embryo (Ericson et al, 1996) or by targeted inactivation in the mouse (Chiang et al, 1996), the floor plate fails to differentiate.…”