Journal article

Lung morphogenesis is orchestrated through Grainyhead-like 2 (Grhl2) transcriptional programs

Ariena Kersbergen, Sarah A Best, Sebastian Dworkin, Casey Ah-Cann, Michael E de Vries, Marie-Liesse Asselin-Labat, Matthew E Ritchie, Stephen M Jane, Kate D Sutherland

DEVELOPMENTAL BIOLOGY | ACADEMIC PRESS INC ELSEVIER SCIENCE | Published : 2018

Abstract

The highly conserved transcription factor Grainyhead-like 2 (Grhl2) exhibits a dynamic expression pattern in lung epithelium throughout embryonic development. Using a conditional gene targeting approach to delete Grhl2 in the developing lung epithelium, our results demonstrate that Grhl2 plays multiple roles in lung morphogenesis that are essential for respiratory function. Loss of Grhl2 leads to impaired ciliated cell differentiation and perturbed formation of terminal saccules. Critically, a substantial increase in Sox9-positive distal tip progenitor cells was observed following loss of Grhl2, suggesting that Grhl2 plays an important role in branching morphogenesis. Gene transcription prof..

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Grants

Awarded by NHMRC Career Development Fellowship


Awarded by NHMRC


Awarded by ARC DECRA grant


Awarded by Victorian Cancer Agency (VCA) Early Career Seed Grant


Funding Acknowledgements

K.D.S is supported by the Peter and Julie Alston Centenary Fellowship; M.E.R is a recipient of an NHMRC Career Development Fellowship (GNT1104924); C. A-C is the recipient of an Australian Lung Foundation Ph.D. Scholarship; S.D and M.E.V are supported by an NHMRC project grant (APP1063837) and an ARC DECRA grant (DE140100500), M-L A-L is supported by a Viertel Foundation Senior Medical Research Fellowship; S.A.B. is supported by a Victorian Cancer Agency (VCA) Early Career Seed Grant (ECSG16001). This work was made possible through Victorian State Government Operational Infrastructure Support and Australian Government.