The transcription factor Gli3 promotes B cell development in fetal liver through repression of Shh

Article


Solanki, Anisha, Lau, Ching-In, Saldaña, J., Ross, Susan and Crompton, Tessa 2017. The transcription factor Gli3 promotes B cell development in fetal liver through repression of Shh. The Journal of Experimental Medicine. 214 (7), pp. 2041 -2058.
AuthorsSolanki, Anisha, Lau, Ching-In, Saldaña, J., Ross, Susan and Crompton, Tessa
Abstract

Before birth, B cells develop in the fetal liver (FL). In this study, we show that Gli3 activity in the FL stroma is required for B cell development. In the Gli3-deficient FL, B cell development was reduced at multiple stages, whereas the Sonic hedgehog (Hh [Shh])–deficient FL showed increased B cell development, and Gli3 functioned to repress Shh transcription. Use of a transgenic Hh-reporter mouse showed that Shh signals directly to developing B cells and that Hh pathway activation was increased in developing B cells from Gli3-deficient FLs. RNA sequencing confirmed that Hh-mediated transcription is increased in B-lineage cells from Gli3-deficient FL and showed that these cells expressed reduced levels of B-lineage transcription factors and B cell receptor (BCR)/pre-BCR–signaling genes. Expression of the master regulators of B cell development Ebf1 and Pax5 was reduced in developing B cells from Gli3-deficient FL but increased in Shh-deficient FL, and in vitro Shh treatment or neutralization reduced or increased their expression, respectively.

JournalThe Journal of Experimental Medicine
Journal citation214 (7), pp. 2041 -2058
ISSN0022-1007
Year2017
PublisherRockefeller University Press
Publisher's version
License
CC BY
File Access Level
Repository staff only
Publisher's version
License
Supplemental file
License
CC BY
Supplemental file
License
CC BY
Digital Object Identifier (DOI)doi:10.1084/jem.20160852
Web address (URL)https://doi.org/10.1084/jem.20160852
Publication dates
Print22 May 2017
Publication process dates
Deposited01 Jun 2017
Accepted10 Apr 2017
Accepted10 Apr 2017
FunderMedical Research Council
Biotechnology and Biological Sciences Research Council
Wellcome Trust
Great Ormond Street Hospital Children’s Charity
National Institute for Health Research
Medical Research Council
Medical Research Council
Biotechnology and Biological Sciences Research Council
Wellcome Trust
Great Ormond Street Hospital Children’s Charity
National Institute for Health Research
Copyright information© 2017 Solanki et. al.
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