Leukocyte receptor tyrosine kinase interacts with secreted midkine to promote survival of migrating neural crest cells

Vieceli, Felipe Monteleone; Bronner, Marianne E.

doi:10.1242/dev.164046

Cited by 13 publications

(6 citation statements)

References 103 publications

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“…Our previously reported modifications in designing individual CRISPR-Cas9 constructs substantially improved gene editing in early chick embryos ( Gandhi et al, 2017 ), allowing successful gene knockouts in numerous studies following electroporation in early embryos ( Gandhi et al, 2020a ; Hutchins and Bronner, 2018 ; Piacentino and Bronner, 2018 ; Tani-Matsuhana et al, 2018 ; Vieceli and Bronner, 2018 ). However, because Cas9 and gRNAs were delivered via separate constructs, a complication was that only cells co-transfected with Cas9 and gRNA plasmids were mutants.…”

Section: Resultsmentioning

confidence: 99%

A single-plasmid approach for genome editing coupled with long-term lineage analysis in chick embryos

Gandhi

Tang

et al. 2021

Development

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An important strategy for establishing mechanisms of gene function during development is through mutation of individual genes and analysis of subsequent effects on cell behavior. Here, we present a single-plasmid approach for genome editing in chick embryos to study experimentally perturbed cells in an otherwise normal embryonic environment. To achieve this, we have engineered a plasmid that encodes Cas9 protein, gene-specific guide RNA (gRNA), and a fluorescent marker within the same construct. Using transfection- and electroporation-based approaches, we show that this construct can be used to perturb gene function in early embryos as well as human cell lines. Importantly, insertion of this cistronic construct into replication-incompetent avian (RIA) retroviruses allowed us to couple gene knockouts with long-term lineage analysis. We demonstrate the application of our newly-engineered constructs and viruses by perturbing β-catenin in vitro and Sox10, Pax6, and Pax7 in the neural crest, retina, neural tube and segmental plate in vivo, respectively. Together, this approach enables knocking out genes of interest in identifiable cells in living embryos and can be broadly applied to numerous genes in different embryonic tissues.

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Section: Resultsmentioning

confidence: 99%

A single-plasmid approach for genome editing coupled with long-term lineage analysis in chick embryos

Gandhi

Tang

et al. 2021

Development

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“…However, in chicken, LTK is more structurally similar to human ALK and could be functionally more similar to human ALK than human LTK. Chicken LTK is expressed in the neural plate border and in migrating cranial and trunk neural crest cells [51].…”

Section: Expression Patterns Of Alkmentioning

confidence: 99%

Defining Pathological Activities of ALK in Neuroblastoma, a Neural Crest-Derived Cancer

Wulf

Moreno

Paka

et al. 2021

IJMS

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Neuroblastoma is a common extracranial solid tumour of childhood, responsible for 15% of cancer-related deaths in children. Prognoses vary from spontaneous remission to aggressive disease with extensive metastases, where treatment is challenging. Tumours are thought to arise from sympathoadrenal progenitor cells, which derive from an embryonic cell population called neural crest cells that give rise to diverse cell types, such as facial bone and cartilage, pigmented cells, and neurons. Tumours are found associated with mature derivatives of neural crest, such as the adrenal medulla or paraspinal ganglia. Sympathoadrenal progenitor cells express anaplastic lymphoma kinase (ALK), which encodes a tyrosine kinase receptor that is the most frequently mutated gene in neuroblastoma. Activating mutations in the kinase domain are common in both sporadic and familial cases. The oncogenic role of ALK has been extensively studied, but little is known about its physiological role. Recent studies have implicated ALK in neural crest migration and sympathetic neurogenesis. However, very few downstream targets of ALK have been identified. Here, we describe pathological activation of ALK in the neural crest, which promotes proliferation and migration, while preventing differentiation, thus inducing the onset of neuroblastoma. Understanding the effects of ALK activity on neural crest cells will help find new targets for neuroblastoma treatment.

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“…Knock-in mice harboring neuroblastoma-associated point mutations of ALK do not exhibit spontaneous tumor formation after birth but show neuronal hyperplasia (Berry et al , 2012; Borenas et al , 2021b; Cazes et al , 2014; Ono et al , 2019). In zebrafish and chicken models, Alk family RTKs are expressed in neural tissues, and have been reported in play a role development of the neural crest (Fadeev et al , 2018; Mo et al , 2017a; Vieceli & Bronner, 2018; Yao et al , 2013) Also, in invertebrate model organisms, such as the fruit fly Drosophila and the nematode C. elegans, Alk/SCD-2 has roles during neurogenesis (Bazigou et al , 2007; Cheng et al , 2011; Gouzi et al , 2011; Pecot et al , 2014). In spite of this, the exact role of ALK in the nervous system and how it relates to development of neuroblastoma is not well understood.…”

Section: Introductionmentioning

confidence: 99%

Patient-associated mutations inDrosophilaAlk perturb neuronal differentiation and promote survival

Pfeifer

Wolfstetter

Anthonydhason

et al. 2022

Preprint

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Activating Anaplastic Lymphoma Kinase (ALK) receptor tyrosine kinase (RTK) mutations occur in pediatric neuroblastoma, and are associated with poor prognosis. To study ALK-activating mutations in a genetically controllable system we employed CRIPSR/Cas9, incorporating orthologues of the human oncogenic mutations ALKF1174L and ALKY1278S in the Drosophila Alk locus. AlkF1251L and AlkY1355S mutant Drosophila exhibit enhanced Alk signaling phenotypes, but unexpectedly depend on the Jelly belly (Jeb) ligand for activation. Both AlkF1251L and AlkY1355S mutant larval brains display hyperplasia, represented by increased numbers of Alk-positive neurons. Despite this hyperplasic phenotype, no brain tumors were observed in mutant animals. We show that hyperplasia in Alk mutants was not caused by significantly increased rates of proliferation, but rather by decreased levels of apoptosis in the larval brain. Using single-cell RNA sequencing (scRNAseq), we have been able to identify perturbations during temporal fate specification in AlkY1355S mutant mushroom body lineages. These findings shed important light on the role of Alk in neurodevelopmental processes and highlight the potential of activating Alk mutations to perturb specification and promote survival in neuronal lineages.

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Leukocyte receptor tyrosine kinase interacts with secreted midkine to promote survival of migrating neural crest cells

Cited by 13 publications

References 103 publications

A single-plasmid approach for genome editing coupled with long-term lineage analysis in chick embryos

A single-plasmid approach for genome editing coupled with long-term lineage analysis in chick embryos

Defining Pathological Activities of ALK in Neuroblastoma, a Neural Crest-Derived Cancer

Patient-associated mutations inDrosophilaAlk perturb neuronal differentiation and promote survival

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