Cooperation of BMP7 and SHH in the Induction of Forebrain Ventral Midline Cells by Prechordal Mesoderm

Abstract

Ventral midline cells at different rostrocaudal levels of the central nervous system exhibit distinct properties but share the ability to pattern the dorsoventral axis of the neural tube. We show here that ventral midline cells acquire distinct identities in response to the different signaling activities of underlying mesoderm. Signals from prechordal mesoderm control the differentiation of rostral diencephalic ventral midline cells, whereas notochord induces floor plate cells caudally. Sonic hedgehog (SHH) is expressed throughout axial mesoderm and is required for the induction of both rostral diencephalic ventral midline cells and floor plate. However, prechordal mesoderm also expresses BMP7 whose function is required coordinately with SHH to induce rostral diencephalic ventral midline cells. BMP7 acts directly on neural cells, modifying their response to SHH so that they differentiate into rostral diencephalic ventral midline cells rather than floor plate cells. Our results suggest a model whereby axial mesoderm both induces the differentiation of overlying neural cells and controls the rostrocaudal character of the ventral midline of the neural tube.

Segregation of Ipsilateral Retinal Ganglion Cell Axons at the Optic Chiasm Requires the Shh Receptor Boc

“…Injection of E13.5 mouse embryos with an hybridoma producing a Shh-blocking antibody (and analyzed at E18.5) alters the distribution of RGC axons at the optic chiasm with an enlargement of the overall region occupied by RGC fibers at the midline and axon extension in aberrant directions. However, as Shh activity is important to pattern the midbrain regions surrounding the ventral hypothalamus (just adjacent to the optic chiasm) during retinal axon development (Dale et al, 1997;Barresi et al, 2005;Manning et al, 2006), it is likely that blocking Shh signaling for 5 d in developing embryos can cause patterning defects. Thus, as noted by the authors (Sánchez-Camacho and Bovolenta, 2008), it is possible that the effects observed are not due to a direct guidance effect of Shh but rather to changes in expression of other guidance cues.…”

Hedgehog signaling in animal development: paradigms and principles

“…Perhaps not surprisingly given their key regulatory actions, misregulation of Hh signaling has been shown to contribute to various pathologies, most notably various cancers including basal cell carci- Bellusci et al 1997;Littingtung et al 1998;Pepicelli et al 1998 Muscle Shh Induction/proliferation/survival epaxial muscle precursors, fiber-type identity, regulation smooth muscle differentiation Johnhson et al 1994;Munsterberg et al 1995;Blagden et al 1997;Duprez et al 1998;Pepicelli et al 1998;Borycki et al 1999;Duprez et al 1999;Lewis et al 1999;Norris et al 2000;Sukegawa et al 2000;Coutelle et al 2001;Kruger et al 2001 Echidna, twhh Muscle/fiber-type identity Currie and Ingham 1996;Du et al 1996 Neural Crest Shh Survival cranial neural crest, cranial facial morphogenesis, proliferation/ differentiation sympathetic cells Helms et al 1997;Ahlgren and Bronner-Fraser 1999;and Williams et al 2000;Garg et al 2001 Neurons Shh Induction of specific ventral neural cell types, proliferation/survival/death neural precursors Echelard et al 1993;Kraus et al 1993;Roelink et al 1994;Ericson et al 1995;Hynes et al 1995;Marti et al 1995;Roelink et al 1995;Wang et al 1995;Belloni et al 1996;Chiang et al 1996;Ericson et al 1997;Dale et al 1997;Kohtz et al 1998;Ye et al 1998;Briscoe et al 1999;…”

Sonic hedgehogRegulates Proliferation and Inhibits Differentiation of CNS Precursor Cells

“…Shh binding to Patched is thought to relieve Patched-mediated inhibition of Smoothened activity, resulting in the activation of transcriptional targets by members of the Gli family (Ingham et al, 1991;for review, see Ingham, 1998). Although Patched and Gli-1 appear to be general transcriptional targets in vertebrates, other factors are specific to neural precursor cells, including HNF3␤ and Nkx-2.2 (Dale et al, 1997;Ericson et al, 1997).…”