Identification of a heterogeneous and dynamic ciliome during embryonic development and cell differentiation

Elliott, Kelsey H.; Balchand, Sai Keshavan; Paese, Christian Louis Bonatto; Chang, Ching-Fang; Yang, Yanfen; Brown, Kari; Rasicci, Daniel T; He, Hao; Thorner, Konrad; Chaturvedi, Praneet; Murray, Stephen A.; Chen, Jing; Porollo, Aleksey; Peterson, Kevin A.; Brugmann, Samantha A.

doi:10.1242/dev.201237

Cited by 4 publications

(3 citation statements)

References 75 publications

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“…Cilia play more indirect roles in regulating other signaling pathways, and the link to cilia is highly context dependent (Lancaster et al., 2011; Ocbina et al., 2009). This is consistent with a growing body of work that suggests cilia are heterogeneous and have tissue‐specific functions (Elliott et al., 2023; O'Hagan et al., 2017; Sun et al., 2019). Cilia heterogeneity is a wide‐open area of research and is ripe for investigation.…”

Section: Discussionsupporting

confidence: 87%

“…These are monogenic disorders with wide‐ranging and overlapping clinical presentations (Reiter & Leroux, 2017). This is in part because of the nearly ubiquitous presence of cilia, with varied composition and function, and in part because cilia are particularly susceptible to genetic modifiers (Elliott et al., 2023). Several ciliopathies present with neurological phenotypes, including structural malformations and intellectual disability (Bisschoff et al., 2013; Poretti et al., 2011).…”

Section: Mainmentioning

confidence: 99%

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Uncovering cilia function in glial development

Bear

Caspary

2023

Annals of Human Genetics

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SUMMARYPrimary cilia play critical roles in regulating signaling pathways that underlie several developmental processes. In the nervous system, cilia are known to regulate signals that guide neuron development. Cilia dysregulation is implicated in neurological diseases, and the underlying mechanisms remain poorly understood. Cilia research has predominantly focused on neurons and has overlooked the diverse population of glial cells in the brain. Glial cells play essential roles during neurodevelopment, and their dysfunction contributes to neurological disease; however, the relationship between cilia function and glial development is understudied. Here we review the state of the field and highlight the glial cell types where cilia are found and the ciliary functions that are linked to glial development. This work uncovers the importance of cilia in glial development and raises outstanding questions for the field. We are poised to make progress in understanding the function of glial cilia in human development and their contribution to neurological diseases.

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Section: Discussionsupporting

confidence: 87%

Section: Mainmentioning

confidence: 99%

Uncovering cilia function in glial development

Bear

Caspary

2023

Annals of Human Genetics

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“…Independent studies such as Syscilia Gold standard ( 82 ), CiliaCarta ( 83 ), and Cildb ( 9 , 84 ) were dedicated to defining the ciliome and identifying candidate ciliary genes using genomic, proteomic, transcriptomic, and evolutionary data, often integrating Bayesian statistics for predictive scoring of ciliary function. Moreover, recent research efforts provided valuable transcriptomic resources for curated primary ciliomes, establishing tissue and temporal specificity within various subgroups of differentially expressed genes associated with ciliary structures ( 85 ).…”

Section: The Roles Of Actin In Ciliogenesismentioning

confidence: 99%

Primary cilia and actin regulatory pathways in renal ciliopathies

Kalot,

Sentell,

Kitzler

et al. 2024

Front. Nephrol.

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Ciliopathies are a group of rare genetic disorders caused by defects to the structure or function of the primary cilium. They often affect multiple organs, leading to brain malformations, congenital heart defects, and anomalies of the retina or skeletal system. Kidney abnormalities are among the most frequent ciliopathic phenotypes manifesting as smaller, dysplastic, and cystic kidneys that are often accompanied by renal fibrosis. Many renal ciliopathies cause chronic kidney disease and often progress to end-stage renal disease, necessitating replacing therapies. There are more than 35 known ciliopathies; each is a rare hereditary condition, yet collectively they account for a significant proportion of chronic kidney disease worldwide. The primary cilium is a tiny microtubule-based organelle at the apex of almost all vertebrate cells. It serves as a “cellular antenna” surveying environment outside the cell and transducing this information inside the cell to trigger multiple signaling responses crucial for tissue morphogenesis and homeostasis. Hundreds of proteins and unique cellular mechanisms are involved in cilia formation. Recent evidence suggests that actin remodeling and regulation at the base of the primary cilium strongly impacts ciliogenesis. In this review, we provide an overview of the structure and function of the primary cilium, focusing on the role of actin cytoskeleton and its regulators in ciliogenesis. We then describe the key clinical, genetic, and molecular aspects of renal ciliopathies. We highlight what is known about actin regulation in the pathogenesis of these diseases with the aim to consider these recent molecular findings as potential therapeutic targets for renal ciliopathies.

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Dynamic enhancer landscapes in human craniofacial development

Rajderkar,

Paraiso,

Amaral

et al. 2024

Nat Commun

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The genetic basis of human facial variation and craniofacial birth defects remains poorly understood. Distant-acting transcriptional enhancers control the fine-tuned spatiotemporal expression of genes during critical stages of craniofacial development. However, a lack of accurate maps of the genomic locations and cell type-resolved activities of craniofacial enhancers prevents their systematic exploration in human genetics studies. Here, we combine histone modification, chromatin accessibility, and gene expression profiling of human craniofacial development with single-cell analyses of the developing mouse face to define the regulatory landscape of facial development at tissue- and single cell-resolution. We provide temporal activity profiles for 14,000 human developmental craniofacial enhancers. We find that 56% of human craniofacial enhancers share chromatin accessibility in the mouse and we provide cell population- and embryonic stage-resolved predictions of their in vivo activity. Taken together, our data provide an expansive resource for genetic and developmental studies of human craniofacial development.

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Identification of a heterogeneous and dynamic ciliome during embryonic development and cell differentiation

Cited by 4 publications

References 75 publications

Uncovering cilia function in glial development

Uncovering cilia function in glial development

Primary cilia and actin regulatory pathways in renal ciliopathies

Dynamic enhancer landscapes in human craniofacial development

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