Neural crest cells utilize primary cilia to regulate ventral forebrain morphogenesis via Hedgehog-dependent regulation of oriented cell division

Schock, Elizabeth N.; Brugmann, Samantha A.

doi:10.1016/j.ydbio.2017.09.026

Cited by 8 publications

(7 citation statements)

References 75 publications

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“…Of all the Hh ligands, SHH is the most studied ligand and acts as a cell–cell signaling factor, modulating cell fates through an autocrine or paracrine mechanism. During embryogenesis, SHH has been shown to be expressed in embryonic structures and involved in pattern formation in the embryo, including the development of the limb at the zone of polarizing activity (ZPA), notochord, or the floor plate of the neural tube [ 38 , 39 ] In addition, SHH is also expressed in the development of the lung [ 40 , 41 ], teeth [ 42 , 43 ], brain [ 44 ], hair follicle [ 45 ], pancreas [ 46 ], and intestine [ 47 ]. IHH is involved in the differentiation and cell fate decision of several specific tissues, including the differentiation of colonic epithelial cells [ 48 , 49 ] and the decision of neuroectodermal cell fate by activating the development of the earliest hemato-vascular system [ 50 ].…”

Section: Elements Of the Hh Signaling Pathwaymentioning

confidence: 99%

Hedgehog Signaling in Cancer: A Prospective Therapeutic Target for Eradicating Cancer Stem Cells

Sari

Phi

Jun

et al. 2018

Cells

154

103

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The Hedgehog (Hh) pathway is a signaling cascade that plays a crucial role in many fundamental processes, including embryonic development and tissue homeostasis. Moreover, emerging evidence has suggested that aberrant activation of Hh is associated with neoplastic transformations, malignant tumors, and drug resistance of a multitude of cancers. At the molecular level, it has been shown that Hh signaling drives the progression of cancers by regulating cancer cell proliferation, malignancy, metastasis, and the expansion of cancer stem cells (CSCs). Thus, a comprehensive understanding of Hh signaling during tumorigenesis and development of chemoresistance is necessary in order to identify potential therapeutic strategies to target various human cancers and their relapse. In this review, we discuss the molecular basis of the Hh signaling pathway and its abnormal activation in several types of human cancers. We also highlight the clinical development of Hh signaling inhibitors for cancer therapy as well as CSC-targeted therapy.

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Section: Elements Of the Hh Signaling Pathwaymentioning

confidence: 99%

Hedgehog Signaling in Cancer: A Prospective Therapeutic Target for Eradicating Cancer Stem Cells

Sari

Phi

Jun

et al. 2018

Cells

154

103

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“…Neural crest mutants exhibit coloboma [ 83 , 84 ], and neural crest cells are implicated in optic fissure closure [ 11 , 15 , 65 – 68 , 70 ]. In mouse, loss of neural crest cilia leads to defective anterior segment development in the eye [ 85 ], and defects in ventral forebrain morphogenesis [ 86 ]. In both cases, Hh signaling in the neural crest cells is lost, and this is thought, at least in part, to contribute to the phenotype: for example, the ventral forebrain phenotype is reproduced via neural crest-specific deletion of Smo .…”

Section: Discussionmentioning

confidence: 99%

Loss of zebrafish dzip1 results in inappropriate recruitment of periocular mesenchyme to the optic fissure and ocular coloboma

2022

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Cilia are essential for the development and function of many different tissues. Although cilia machinery is crucial in the eye for photoreceptor development and function, a role for cilia in early eye development and morphogenesis is still somewhat unclear: many zebrafish cilia mutants retain cilia at early stages due to maternal deposition of cilia components. An eye phenotype has been described in the mouse Arl13 mutant, however, zebrafish arl13b is maternally deposited, and an early role for cilia proteins has not been tested in zebrafish eye development. Here we use the zebrafish dzip1 mutant, which exhibits a loss of cilia throughout stages of early eye development, to examine eye development and morphogenesis. We find that in dzip1 mutants, initial formation of the optic cup proceeds normally, however, the optic fissure subsequently fails to close and embryos develop the structural eye malformation ocular coloboma. Further, neural crest cells, which are implicated in optic fissure closure, do not populate the optic fissure correctly, suggesting that their inappropriate localization may be the underlying cause of coloboma. Overall, our results indicate a role for dzip1 in proper neural crest localization in the optic fissure and optic fissure closure.

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“…ImageJ to measure the tdTomato+ neuroectodermal length of ventricle to normalize embryonic PH3 quantification 65 ( Fig. 1H ) and body lengths of P30 control and mutants across both sexes to evaluate stature 60 ( Supplementary Data 6A , B ).…”

Section: Methods Detailsmentioning

confidence: 99%

Integrity of the minor spliceosome in the developing mouse hypothalamus determines neuronal subtype composition regulating energy balance

White

Drake

Porczak

et al. 2022

Preprint

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While gene regulatory networks underlying hypothalamic development are being characterized, minor intron splicing remains unexplored. Here, we used Nkx2.1-Cre to ablate Rnu11, encoding the minor spliceosome-specific U11 snRNA, in the progenitors of the ventral diencephalon (VD), to study minor intron splicing in hypothalamic development and control of energy balance in mice. Loss of U11 resulted in aberrant minor intron splicing, mitotic stalling, apoptosis, and altered neurogenesis. Mutant mice exhibited gross dysgenesis of hypothalamic architecture, while single-cell RNA sequencing (scRNAseq) revealed aberrant composition of neuronal subtypes implicated in feeding and energy balance. Mutant weanlings failed to thrive, followed by rapid weight gain, resulting in obesity. Assessment of energy imbalance and pair-feeding demonstrated that hyperphagia in adult mutants initiates weight gain, and is compounded by metabolic dysfunction, ultimately resulting in obesity. Our findings suggest a key role of minor intron splicing in the developmental patterning of hypothalamic neuronal subtypes underlying energy balance.

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Neural crest cells utilize primary cilia to regulate ventral forebrain morphogenesis via Hedgehog-dependent regulation of oriented cell division

Cited by 8 publications

References 75 publications

Hedgehog Signaling in Cancer: A Prospective Therapeutic Target for Eradicating Cancer Stem Cells

Hedgehog Signaling in Cancer: A Prospective Therapeutic Target for Eradicating Cancer Stem Cells

Loss of zebrafish dzip1 results in inappropriate recruitment of periocular mesenchyme to the optic fissure and ocular coloboma

Integrity of the minor spliceosome in the developing mouse hypothalamus determines neuronal subtype composition regulating energy balance

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