Decision letter: Critical role of WNK1 in MYC-dependent early mouse thymocyte development

Critical role of WNK1 in MYC-dependent early mouse thymocyte development

eLife ◽

10.7554/elife.56934 ◽

2020 ◽

Vol 9 ◽

Author(s):

Robert Köchl ◽

Lesley Vanes ◽

Miriam Llorian Sopena ◽

Probir Chakravarty ◽

Harald Hartweger ◽

...

Keyword(s):

Critical Role ◽

Ion Homeostasis ◽

Thymocyte Development ◽

Double Positive ◽

Mouse Thymocyte ◽

Proliferation And Differentiation ◽

Tcr Signals ◽

And Migration ◽

Early Mouse

WNK1, a kinase that controls kidney salt homeostasis, also regulates adhesion and migration in CD4+ T cells. Wnk1 is highly expressed in thymocytes, and since migration is important for thymocyte maturation, we investigated a role for WNK1 in mouse thymocyte development. We find that WNK1 is required for the transition of double negative (DN) thymocytes through the β-selection checkpoint and subsequent proliferation and differentiation into double positive (DP) thymocytes. Furthermore, we show that WNK1 negatively regulates LFA1-mediated adhesion and positively regulates CXCL12-induced migration in DN thymocytes. Despite this, migration defects of WNK1-deficient thymocytes do not account for the developmental arrest. Instead, we show that in DN thymocytes WNK1 transduces pre-TCR signals via OXSR1 and STK39 kinases, and the SLC12A2 ion co-transporter that are required for post-transcriptional upregulation of MYC and subsequent proliferation and differentiation into DP thymocytes. Thus, a pathway regulating ion homeostasis is a critical regulator of thymocyte development.

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Author response: Critical role of WNK1 in MYC-dependent early mouse thymocyte development

10.7554/elife.56934.sa2 ◽

2020 ◽

Author(s):

Robert Köchl ◽

Lesley Vanes ◽

Miriam Llorian Sopena ◽

Probir Chakravarty ◽

Harald Hartweger ◽

...

Keyword(s):

Critical Role ◽

Author Response ◽

Thymocyte Development ◽

Mouse Thymocyte ◽

Early Mouse

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Critical role of WNK1 in MYC-dependent early thymocyte development

10.1101/2020.06.11.147017 ◽

2020 ◽

Author(s):

Robert Köchl ◽

Lesley Vanes ◽

Miriam Llorian Sopena ◽

Probir Chakravarty ◽

Harald Hartweger ◽

...

Keyword(s):

Critical Role ◽

Ion Homeostasis ◽

Thymocyte Development ◽

Double Positive ◽

Developmental Arrest ◽

Proliferation And Differentiation ◽

Tcr Signals ◽

And Migration ◽

Salt Homeostasis

AbstractWNK1, a kinase that controls kidney salt homeostasis, also regulates adhesion and migration in CD4+ T cells. Wnk1 is highly expressed in thymocytes, and since migration is important for thymocyte maturation, we investigated a role for WNK1 in thymocyte development. We find that WNK1 is required for the transition of double negative (DN) thymocytes through the β-selection checkpoint and subsequent proliferation and differentiation into double positive (DP) thymocytes. Furthermore, we show that WNK1 negatively regulates LFA1-mediated adhesion and positively regulates CXCL12-induced migration in DN thymocytes. Despite this, migration defects of WNK1-deficient thymocytes do not account for the developmental arrest. Instead, we show that in DN thymocytes WNK1 transduces pre-TCR signals via OXSR1 and STK39 kinases and the SLC12A2 ion co-transporter that are required for post-transcriptional upregulation of MYC and subsequent proliferation and differentiation into DP thymocytes. Thus, a pathway regulating ion homeostasis is a critical regulator of thymocyte development.

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The Role of the SLP in Autism Spectrum Disorder Screening and Assessment

Perspectives on Language Learning and Education ◽

10.1044/lle15.2.50 ◽

2008 ◽

Vol 15 (2) ◽

pp. 50-59 ◽

Cited By ~ 1

Author(s):

Amy Philofsky

Keyword(s):

Language Development ◽

Critical Role ◽

Children With Autism ◽

Autism Spectrum ◽

Children With Asd ◽

Prevalence Estimates ◽

Notable Increase ◽

Screening Assessment ◽

Critical Components

AbstractRecent prevalence estimates for autism have been alarming as a function of the notable increase. Speech-language pathologists play a critical role in screening, assessment and intervention for children with autism. This article reviews signs that may be indicative of autism at different stages of language development, and discusses the importance of several psychometric properties—sensitivity and specificity—in utilizing screening measures for children with autism. Critical components of assessment for children with autism are reviewed. This article concludes with examples of intervention targets for children with ASD at various levels of language development.

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