Embigin deficiency leads to delayed embryonic lung development and high neonatal mortality in mice

Salli Talvi; Johanna Jokinen; Kalle Sipilä; Pekka Rappu; Fu-Ping Zhang; Matti Poutanen; Pia Rantakari; Jyrki Heino

doi:10.1016/j.isci.2024.108914

Embigin deficiency leads to delayed embryonic lung development and high neonatal mortality in mice

iScience. 2024 Jan 15;27(2):108914. doi: 10.1016/j.isci.2024.108914. eCollection 2024 Feb 16.

Authors

Salli Talvi^{1

2

3}, Johanna Jokinen^{1

2

3}, Kalle Sipilä^{1

4}, Pekka Rappu^{1

3}, Fu-Ping Zhang^{5

6

7}, Matti Poutanen^{3

5

6}, Pia Rantakari^{3

8

9}, Jyrki Heino^{1

2

3}

Affiliations

¹ Department of Life Technologies, University of Turku, 20014 Turku, Finland.
² Medicity Research Laboratory, University of Turku, 20014 Turku, Finland.
³ InFLAMES Research Flagship, University of Turku, 20014 Turku, Finland.
⁴ Centre for Stem Cells and Regenerative Medicine, King's College London, London WC2R2LS, UK.
⁵ Institute of Biomedicine, Research Centre for Integrative Physiology and Pharmacology, University of Turku, 20014 Turku, Finland.
⁶ Turku Center for Disease Modeling, University of Turku, 20014 Turku, Finland.
⁷ Helsinki Institute of Life Science, University of Helsinki, 00014 Helsinki, Finland.
⁸ Institute of Biomedicine, University of Turku, 20014 Turku, Finland.
⁹ Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20014 Turku, Finland.

Abstract

Embigin (Gp70), a receptor for fibronectin and an ancillary protein for monocarboxylate transporters, is known to regulate stem cell niches in sebaceous gland and bone marrow. Here, we show that embigin expression is at high level during early mouse embryogenesis and that embigin is essential for lung development. Markedly increased neonatal mortality of Emb^-/- mice can be explained by the compromised lung maturation: in Emb^-/- mice (E17.5) the number and the size of the small airways and distal airspace are significantly smaller, there are fewer ATI and ATII cells, and the alkaline phosphatase activity in amniotic fluid is lower. Emb^-/- lungs show less peripheral branching already at E12.5, and embigin is highly expressed in lung primordium. Thus, embigin function is essential at early pseudoglandular stage or even earlier. Furthermore, our RNA-seq analysis and Ki67 staining results support the idea that the development of Emb^-/- lungs is rather delayed than defected.

Keywords: Developmental biology; Developmental genetics; Transcriptomics.