Knockdown of slit signaling during limb development leads to a reduction in humerus length

Rafipay, Alexandra; Dun, Xin‐Peng; Parkinson, David B.; Erskine, Lynda; Vargesson, Neil

doi:10.1002/dvdy.284

Cited by 8 publications

(8 citation statements)

References 64 publications

(196 reference statements)

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“…SLIT3 is one of the three SLIT ligands identified in the central nervous system, expressed and involved in muscle development and bone formation ( 40 ), angiogenesis ( 41 ), and stem cell migration ( 42 ), which are widely expressed in various cell types during embryogenesis and are involved in basic aspects of limb development. Knockdown of individual SLIT genes or Slit1 and Slit2 in combination resulted in a shortening of the length of the humerus ( 43 ). Kim et al ( 44 ) found that β-catenin knockdown completely blocked Slit3-stimulated osteoblast migration and proliferation.…”

Section: Discussionmentioning

confidence: 99%

Genome-Wide Association Study of Egg-Laying Traits and Egg Quality in LingKun Chickens

Gao

Zeng

et al. 2022

Front. Vet. Sci.

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Egg production is the most important trait of laying hens. To identify molecular markers and candidate genes associated with egg production and quality, such as body weight at first oviposition (BWF), the number of eggs produced in 500 days (EN500), egg weight (EW), egg shell thickness (EST), egg shell strength (ESS), and Haugh unit (HU), a genome-wide analysis was performed in 266 LingKun Chickens. The results showed that thirty-seven single nucleotide polymorphisms (SNPs) were associated with all traits (p < 9.47 × 10−8, Bonferroni correction). These SNPs were located in close proximity to or within the sequence of the thirteen candidate genes, such as Galanin And GMAP Prepropeptide (GAL), Centromere Protein (CENPF), Glypican 2 (GPC2), Phosphatidylethanolamine N-Methyltransferase (PEMT), Transcription Factor AP-2 Delta (TFAP2D), and Carboxypeptidase Q (CPQ) gene related to egg-laying and Solute Carrier Family 5 Member 7 (SLC5A7), Neurocalcin Delta (NCALD), Proteasome 20S Subunit Beta 2 (PSMB2), Slit Guidance Ligand 3 (SLIT3), and Tubulin Tyrosine Ligase Like 7 (TTLL7) genes related to egg quality. Interestingly, one of the genes involved in bone formation (SLIT3) was identified as a candidate gene for ESS. Our candidate genes and SNPs associated with egg-laying traits were significant for molecular breeding of egg-laying traits and egg quality in LingKun chickens.

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Section: Discussionmentioning

confidence: 99%

Genome-Wide Association Study of Egg-Laying Traits and Egg Quality in LingKun Chickens

Gao

Zeng

et al. 2022

Front. Vet. Sci.

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“…Decreased expression of Znf536 may enhance neuronal differentiation 78 . Intriguingly, Slit1 is enriched in the prefrontal cortex of monkeys but is not detected during mouse limb development 79,80 . In contrast, gene function enrichment at the latter time point included chondrocyte development, osteoblast proliferation and collagen organization (Figure 6H).…”

Section: Limb Bud Development In Larval-stage Neotenic Axolotlsmentioning

confidence: 99%

The single-cell transcriptional landscape of the axolotl

Zhang

Weigao

et al. 2021

Preprint

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The Mexican axolotl (Ambystoma mexicanum) is a promising tetrapod model for regeneration and developmental studies. Remarkably, neotenic axolotls may undergo metamorphosis, during which their regeneration capacity and lifespan gradually decline. However, a system-level single-cell analysis of molecular characteristics in neotenic and metamorphosed axolotls is still lacking. Here, we developed a single-cell RNA-seq method based on combinatorial hybridization to generate a tissue-based transcriptomic atlas of the adult axolotl. We performed gene expression profiling of over 1 million single cells across 19 tissues to construct the first adult axolotl cell atlas. Comparison of single-cell transcriptomes between the tissues of neotenic and metamorphosed axolotls revealed the heterogeneity of structural cells in different tissues and established their regulatory network. Furthermore, we described dynamic gene expression patterns during limb development in neotenic axolotls. These data serve as a resource to explore the molecular identity of the axolotl as well as its metamorphosis.

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“…The semaphorins and the slit/robo genes are prominent examples. (1)(2)(3)(4)(5)(6)(7)(8)(9) Intriguingly, lower bone mineral density (BMD) and increased risk of fractures have been observed in both children and young adults with autism spectrum disorder syndromes (ASDs). (10)(11)(12) Mutations in SH3 and multiple Ankyrin repeat domain protein 2 (Shank2), originally identified as cortactin-binding protein 1 (CortBP1) or proline rich synapse associated protein 1 (Pro-SAP1), have been reported to be associated with ASDs.…”

Section: Introductionmentioning

confidence: 99%

“…The semaphorins and the slit/robo genes are prominent examples. ( 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 )…”

Section: Introductionmentioning

confidence: 99%

Downregulation of the Autism Spectrum Disorder Gene Shank2 Decreases Bone Mass in Male Mice

et al. 2022

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Mutations of the postsynaptic scaffold protein Shank2 lead to autism spectrum disorders (ASD). These patients frequently suffer from higher fracture risk. Here, we investigated whether Shank2 directly regulates bone mass. We show that Shank2 is expressed in bone and that Shank2 levels are increased during osteoblastogenesis. Knockdown of Shank2 by siRNA targeting the encoding regions for PDZ and SAM domain inhibits osteoblastogenesis of primary murine calvarial osteoblasts. Shank2 knockout mice (Shank2 À/À ) have a decreased bone mass due to reduced osteoblastogenesis and bone formation, whereas bone resorption remains unaffected. Induced pluripotent stem cells (iPSCs)-derived osteoblasts from a loss-of-function Shank2 mutation in a patient showed a significantly reduced osteoblast differentiation potential. Moreover, silencing of known Shank2 interacting proteins revealed that a majority of them promote osteoblast differentiation. From this we conclude that Shank2 and interacting proteins known from the central nervous system are decisive regulators in osteoblast differentiation.

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Knockdown of slit signaling during limb development leads to a reduction in humerus length

Cited by 8 publications

References 64 publications

Genome-Wide Association Study of Egg-Laying Traits and Egg Quality in LingKun Chickens

Genome-Wide Association Study of Egg-Laying Traits and Egg Quality in LingKun Chickens

The single-cell transcriptional landscape of the axolotl

Downregulation of the Autism Spectrum Disorder Gene Shank2 Decreases Bone Mass in Male Mice

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