Sonic hedgehog is a chemotactic neural crest cell guide that is perturbed by ethanol exposure

Tolosa, Ezequiel J.; Fernández-Zapico, Martín E.; Battiato, Natalia Laura; Rovasio, Roberto A.

doi:10.1016/j.ejcb.2016.02.003

Cited by 19 publications

(19 citation statements)

References 84 publications

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“…Complementary work has shown that Vegfa is also an essential growth factor secreted by Hox-negative NC mesenchyme, and we have shown here that this gene is less expressed in severely affected Wnt1-Cre;CAG-Hoxb1 mutant heads; its homozygous loss from the same population leads to cleft palate, reduced ossification of the premaxillary and frontal bones, and maxillary hypoplasia preceded by reduced vascular growth within PA1 (Wiszniak et al, 2015). Vegfa is also chemotactic for NC cells and Another chemotactic factor for cephalic NC is Sonic hedgehog, in particular for mesencephalic NC surrounding the optic vesicles (Tolosa, Fernández-Zapico, Battiato, & Rovasio, 2016). Shh is also a survival factor for Hox-negative NC cells (Ahlgren & Bronner-Fraser, 1999).…”

Section: Discussionmentioning

confidence: 69%

Ectopic expression of Hoxb1 induces cardiac and craniofacial malformations

Zaffran

Odelin

Stefanovic

et al. 2018

Genesis

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Members of the large family of Hox transcription factors are encoded by genes whose tightly regulated expression in development and in space within different embryonic tissues confer positional identity from the neck to the tips of the limbs. Many structures of the face, head, and heart develop from cell populations expressing few or no Hox genes. Hoxb1 is the member of its chromosomal cluster expressed in the most rostral domain during vertebrate development, but never by the multipotent neural crest cell population anterior to the cerebellum. We have developed a novel floxed transgenic mouse line, CAG-Hoxb1,-EGFP (CAG-Hoxb1), which upon recombination by Cre recombinase conditionally induces robust Hoxb1 and eGFP overexpression. When induced within the neural crest lineage, pups die at birth. A variable phenotype develops from E11.5 on, associating frontonasal hypoplasia/aplasia, micrognathia/agnathia, major ocular and forebrain anomalies, and cardiovascular malformations. Neural crest derivatives in the body appear unaffected. Transcription of effectors of developmental signaling pathways (Bmp, Shh, Vegfa) and transcription factors (Pax3, Sox9) is altered in mutants. These outcomes emphasize that repression of Hoxb1, along with other paralog group 1 and 2 Hox genes, is strictly necessary in anterior cephalic NC for craniofacial, visual, auditory, and cardiovascular development.

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Section: Discussionmentioning

confidence: 69%

Ectopic expression of Hoxb1 induces cardiac and craniofacial malformations

Zaffran

Odelin

Stefanovic

et al. 2018

Genesis

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“…There is very little known about the role of Hedgehog family proteins (Sonic and Indian) in NPB and NC cell specification, although there is more known about their role in NC migration (Powell et al, 2015; Testaz et al, 2001; Tolosa, Fernandez-Zapico, Battiato, & Rovasio, 2016). However, two recent studies have begun to dissect the function of Hedgehog ligands and effectors in these early developmental processes.…”

Section: | Signaling Events Regulating Nc Inductionmentioning

confidence: 99%

Specifying neural crest cells: From chromatin to morphogens and factors in between

Rogers

Nie

2018

WIREs Developmental Biology

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Neural crest (NC) cells are a stem-like multipotent population of progenitor cells that are present in vertebrate embryos, traveling to various regions in the developing organism. Known as the "fourth germ layer", these cells originate in the ectoderm between the neural plate (NP), which will become the brain and spinal cord, and nonneural tissues that will become the skin and the sensory organs. NC cells can differentiate into more than 30 different derivatives in response to the appropriate signals including, but not limited to, craniofacial bone and cartilage, sensory nerves and ganglia, pigment cells, and connective tissue. The molecular and cellular mechanisms that control the induction and specification of NC cells include epigenetic control, multiple interactive and redundant transcriptional pathways, secreted signaling molecules, and adhesion molecules. NC cells are important not only because they transform into a wide variety of tissue types, but also because their ability to detach from their epithelial neighbors and migrate throughout developing embryos utilizes mechanisms similar to those used by metastatic cancer cells. In this review, we discuss the mechanisms required for the induction and specification of NC cells in various vertebrate species, focusing on the roles of early morphogenesis, cell adhesion, signaling from adjacent tissues, and the massive transcriptional network that controls the formation of these amazing cells. This article is categorized under: Nervous System Development > Vertebrates: General Principles Gene Expression and Transcriptional Hierarchies > Regulatory Mechanisms Gene Expression and Transcriptional Hierarchies > Gene Networks and Genomics Signaling Pathways > Cell Fate Signaling.

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“…These alterations commonly disrupt neurological function and behavior, and in severe cases, lead to structural abnormalities, such as agenesis of the corpus callosum and cerebellar hypoplasia (Mattson and Riley, 1996;Lemoine et al, 2003;Sokol, 2003;Hoyme et al, 2005;Riley et al, 2011). In the adjacent neural crest, early exposure to ETOH decreases delamination, inhibits proliferation, decreases survival, and alters migration (Garic-Stankovic et al, 2005;Flentke et al, 2011;Garic et al, 2011;Smith et al, 2014;Tolosa et al, 2016), resulting in the classic craniofacial anomalies associated with FAS (e.g., thin vermillion, shortened palpebral fissures, and smooth philtrum), and also causing cleft lip and cleft palate in severe cases (Hoyme et al, 2005;Klingenberg et al, 2010;Riley et al, 2011;Foroud et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Differences in neural crest sensitivity to ethanol account for the infrequency of anterior segment defects in the eye compared with craniofacial anomalies in a zebrafish model of fetal alcohol syndrome

Eason

Williams

Chawla

et al. 2017

Birth Defects Research

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Background Ethanol (ETOH) exposure during pregnancy is associated with craniofacial and neurologic abnormalities, but infrequently disrupts the anterior segment of the eye. In these studies, we used zebrafish to investigate differences in the teratogenic effect of ETOH on craniofacial, periocular, and ocular neural crest. Methods Zebrafish eye and neural crest development was analyzed via live imaging, TUNEL assay, immunostaining, detection of reactive oxygen species, and in situ hybridization. Results Our studies demonstrated that foxd3-positive neural crest cells in the periocular mesenchyme and developing eye were less sensitive to ETOH than sox10-positive craniofacial neural crest cells that form the pharyngeal arches and jaw. ETOH increased apoptosis in the retina, but did not affect survival of periocular and ocular neural crest cells. ETOH also did not increase reactive oxygen species within the eye. In contrast, ETOH increased ventral neural crest apoptosis and reactive oxygen species production in the facial mesenchyme. In the eye and craniofacial region, sod2 showed high levels of expression in the anterior segment and in the setting of Sod2 knockdown, low levels of ETOH decreased migration of foxd3-positive neural crest cells into the developing eye. However, ETOH had minimal effect on the periocular and ocular expression of transcription factors (pitx2 and foxc1) that regulate anterior segment development. Conclusions Neural crest cells contributing to the anterior segment of the eye exhibit increased ability to withstand ETOH-induced oxidative stress and apoptosis. These studies explain the rarity of anterior segment dysgenesis despite the frequent craniofacial abnormalities in fetal alcohol syndrome.

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Sonic hedgehog is a chemotactic neural crest cell guide that is perturbed by ethanol exposure

Cited by 19 publications

References 84 publications

Ectopic expression of Hoxb1 induces cardiac and craniofacial malformations

Ectopic expression of Hoxb1 induces cardiac and craniofacial malformations

Specifying neural crest cells: From chromatin to morphogens and factors in between

Differences in neural crest sensitivity to ethanol account for the infrequency of anterior segment defects in the eye compared with craniofacial anomalies in a zebrafish model of fetal alcohol syndrome

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