13-P065 How long does ventral neural tube patterning need Sonic Hedgehog signaling?

Floor plate cells at the midline of the neural tube are specified by high-level activity of Sonic hedgehog (Shh) secreted by notochord, whereas motor neurons are thought to be specified by a lower level activity of Shh secreted in turn by floor plate cells. In Drosophila, the Gli zinc finger protein Cubitus interruptus functions as a transcription factor activating Hedgehog-responsive genes. We report that the expression of known Shh-responsive genes such as Ptc and Gli1 is downregulated in mutant mice lacking Gli2 function. Gli2 mutants fail to develop a floor plate yet still develop motor neurons, which occupy the ventral midline of the neural tube. Our results imply that Gli2 is required to mediate high level but not low level Shh activity and show that the development of motor neurons can occur in the absence of floor plate induction.

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Sonic hedgehog signaling at gastrula stages specifies ventral telencephalic cells in the chick embryo

Development ◽

10.1242/dev.127.15.3283 ◽

2000 ◽

Vol 127 (15) ◽

pp. 3283-3293 ◽

Cited By ~ 3

Author(s):

L. Gunhaga ◽

T.M. Jessell ◽

T. Edlund

Keyword(s):

Sonic Hedgehog ◽

Neural Tube ◽

Hedgehog Signaling ◽

Early Stage ◽

Primitive Streak ◽

Cell Types ◽

Neural Cells ◽

Sonic Hedgehog Signaling ◽

Ventral Telencephalon ◽

Prechordal Mesoderm

A secreted signaling factor, Sonic hedgehog (Shh), has a crucial role in the generation of ventral cell types along the entire rostrocaudal axis of the neural tube. At caudal levels of the neuraxis, Shh is secreted by the notochord and floor plate during the period that ventral cell fates are specified. At anterior prosencephalic levels that give rise to the telencephalon, however, neither the prechordal mesoderm nor the ventral neural tube expresses Shh at the time that the overt ventral character of the telencephalon becomes evident. Thus, the precise role and timing of Shh signaling relevant to the specification of ventral telencephalic identity remains unclear. By analysing neural cell differentiation in chick neural plate explants we provide evidence that neural cells acquire molecular properties characteristic of the ventral telencephalon in response to Shh signals derived from the anterior primitive streak/Hensen's node region at gastrula stages. Exposure of prospective anterior prosencephalic cells to Shh at this early stage is sufficient to initiate a temporal program of differentiation that parallels that of neurons generated normally in the medial ganglionic eminence subdivision of the ventral telencephalon.

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Sonic hedgehog and the molecular regulation of mouse neural tube closure

Development ◽

10.1242/dev.129.10.2507 ◽

2002 ◽

Vol 129 (10) ◽

pp. 2507-2517 ◽

Cited By ~ 8

Author(s):

Patricia Ybot-Gonzalez ◽

Patricia Cogram ◽

Dianne Gerrelli ◽

Andrew J. Copp

Keyword(s):

Sonic Hedgehog ◽

Neural Tube ◽

Hedgehog Signaling ◽

Neural Plate ◽

Neural Tube Closure ◽

Molecular Regulation ◽

Sonic Hedgehog Signaling ◽

Surface Ectoderm ◽

Necessary And Sufficient ◽

Tube Closure

Neural tube closure is a fundamental embryonic event whose molecular regulation is poorly understood. As mouse neurulation progresses along the spinal axis, there is a shift from midline neural plate bending to dorsolateral bending. Here, we show that midline bending is not essential for spinal closure since, in its absence, the neural tube can close by a ‘default’ mechanism involving dorsolateral bending, even at upper spinal levels. Midline and dorsolateral bending are regulated by mutually antagonistic signals from the notochord and surface ectoderm. Notochordal signaling induces midline bending and simultaneously inhibits dorsolateral bending. Sonic hedgehog is both necessary and sufficient to inhibit dorsolateral bending, but is neither necessary nor sufficient to induce midline bending, which seems likely to be regulated by another notochordal factor. Attachment of surface ectoderm cells to the neural plate is required for dorsolateral bending, which ensures neural tube closure in the absence of sonic hedgehog signaling.

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Gene Regulatory Logic for Reading the Sonic Hedgehog Signaling Gradient in the Vertebrate Neural Tube

Cell ◽

10.1016/j.cell.2011.10.047 ◽

2012 ◽

Vol 148 (1-2) ◽

pp. 273-284 ◽

Cited By ~ 282

Author(s):

Nikolaos Balaskas ◽

Ana Ribeiro ◽

Jasmina Panovska ◽

Eric Dessaud ◽

Noriaki Sasai ◽

...

Keyword(s):

Sonic Hedgehog ◽

Neural Tube ◽

Hedgehog Signaling ◽

Sonic Hedgehog Signaling ◽

Gene Regulatory

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A gradient of Gli activity mediates graded Sonic Hedgehog signaling in the neural tube

Genes & Development ◽

10.1101/gad.325905 ◽

2005 ◽

Vol 19 (5) ◽

pp. 626-641 ◽

Cited By ~ 172

Author(s):

D. Stamataki

Keyword(s):

Sonic Hedgehog ◽

Neural Tube ◽

Hedgehog Signaling ◽

Sonic Hedgehog Signaling

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Zebrafishsmoothenedfunctions in ventral neural tube specification and axon tract formation

Development ◽

10.1242/dev.128.18.3497 ◽

2001 ◽

Vol 128 (18) ◽

pp. 3497-3509 ◽

Cited By ~ 16

Author(s):

Zoltán M. Varga ◽

Angel Amores ◽

Katharine E. Lewis ◽

Yi-Lin Yan ◽

John H. Postlethwait ◽

...

Keyword(s):

Sonic Hedgehog ◽

Neural Tube ◽

Hedgehog Signaling ◽

Floor Plate ◽

Slow Muscle ◽

Pituitary Cells ◽

Shh Signaling ◽

Ventral Neural Tube ◽

Hypothalamic Cells

Sonic hedgehog (Shh) signaling patterns many vertebrate tissues. shh mutations dramatically affect mouse ventral forebrain and floor plate but produce minor defects in zebrafish. Zebrafish have two mammalian Shh orthologs, sonic hedgehog and tiggy-winkle hedgehog, and another gene, echidna hedgehog, that could have overlapping functions. To examine the role of Hedgehog signaling in zebrafish, we have characterized slow muscle omitted (smu) mutants. We show that smu encodes a zebrafish ortholog of Smoothened that transduces Hedgehog signals. Zebrafish smoothened is expressed maternally and zygotically and supports specification of motoneurons, pituitary cells and ventral forebrain. We propose that smoothened is required for induction of lateral floor plate and a subpopulation of hypothalamic cells and for maintenance of medial floor plate and hypothalamic cells.

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