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Inhibition of Sonic hedgehog signaling in vivo results in craniofacial neural crest cell death

Ahlgren, Sara C. and Bronner-Fraser, Marianne (1999) Inhibition of Sonic hedgehog signaling in vivo results in craniofacial neural crest cell death. Current Biology, 9 (22). pp. 1304-1314. ISSN 0960-9822. doi:10.1016/S0960-9822(00)80052-4.

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Background: Sonic hedgehog (Shh) is well known for its role in patterning tissues, including structures of the head. Haploinsufficiency for SHH in humans results in holoprosencephaly, a syndrome characterized by facial and forebrain abnormalities. Shh null mice have cyclopia and loss of branchial arch structures. It is unclear, however, whether these phenotypes arise solely from the early function of Shh in patterning midline structures, or whether Shh plays other roles in head development. Results: To address the role of Shh after floorplate induction, we inhibited Shh signaling by injecting hybridoma cells that secrete a function-blocking anti-Shh antibody into the chick cranial mesenchyme. The antibody subsequently bound to Shh in the floorplate, notochord, and the pharyngeal endoderm. Perturbation of Shh signaling at this stage resulted in a significant reduction in head size after 1 day, loss of branchial arch structures after 2 days, and embryos with smaller heads after 7 days. Cell death was significantly increased in the neural tube and neural crest after 1 day, and neural crest cell death was not secondary to the loss of neural tube cells. Conclusions: Reduction of Shh signaling after neural tube closure resulted in a transient decrease in neural tube cell proliferation and an extensive increase in cell death in the neural tube and neural crest, which in turn resulted in decreased head size. The phenotypes observed after reduction of Shh are similar to those observed after cranial neural crest ablation. Thus, our results demonstrate a role for Shh in coordinating the proliferation and survival of cells of the neural tube and cranial neural crest.

Item Type:Article
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Bronner-Fraser, Marianne0000-0003-4274-1862
Additional Information:© 1999 Elsevier Science Ltd. Received: 8 February 1999. Revised: 1 September 1999. Accepted: 4 October 1999. Published: 3 November 1999. Available online 15 January 2001. The authors wish to thank Clare Baker and Andy Groves for critical readings of this manuscript, and Christophe Marcelle for helpful discussions during the course of the experiments. Cliff Tabin kindly supplied the chicken Ptc and Shh probes. S.C.A. was supported by NIH award # NS07251 and the American Heart Association award # 1168-F1. This work was supported by USPHS NS34671 and NS36585.
Funding AgencyGrant Number
American Heart Association1168-F1
U.S. Public Health Service (USPHS)NS34671
U.S. Public Health Service (USPHS)NS36585
Issue or Number:22
Record Number:CaltechAUTHORS:20160323-142432720
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Official Citation:Sara C. Ahlgren, Marianne Bronner-Fraser, Inhibition of Sonic hedgehog signaling in vivo results in craniofacial neural crest cell death, Current Biology, Volume 9, Issue 22, 18 November 1999, Pages 1304-1314, ISSN 0960-9822, (
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:65634
Deposited By: Ruth Sustaita
Deposited On:24 Mar 2016 17:33
Last Modified:10 Nov 2021 23:48

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