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First published online December 7, 2008
doi: 10.1242/10.1242/dev.028456

Development 136, 29-34 (2009)
Published by The Company of Biologists 2009
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Research Report

Lymph sacs are not required for the initiation of lymph node formation

Mark F. Vondenhoff1,*, Serge A. van de Pavert1,*, Miriam E. Dillard2, Mascha Greuter1, Gera Goverse1, Guillermo Oliver2,{dagger} and Reina E. Mebius1,{dagger}

1 Department of Molecular Cell Biology and Immunology, VU University Medical Center, PO box 7057, 1007 MB Amsterdam, The Netherlands.
2 Department of Genetics and Tumor Cell Biology, St Jude Children's Research Hospital, Memphis, TN 38105, USA.

{dagger} Authors for correspondence (e-mails: guillermo.oliver{at}stjude.org; r.mebius{at}vumc.nl)

Accepted 28 October 2008

SUMMARY

The lymphatic vasculature drains lymph fluid from the tissue spaces of most organs and returns it to the blood vasculature for recirculation. Before reaching the circulatory system, antigens and pathogens transported by the lymph are trapped by the lymph nodes. As proposed by Florence Sabin more than a century ago and recently validated, the mammalian lymphatic vasculature has a venous origin and is derived from primitive lymph sacs scattered along the embryonic body axis. Also as proposed by Sabin, it has been generally accepted that lymph nodes originate from those embryonic primitive lymph sacs. However, we now demonstrate that the initiation of lymph node development does not require lymph sacs. We show that lymph node formation is initiated normally in E14.5 Prox1-null mouse embryos devoid of lymph sacs and lymphatic vasculature, and in E17.5 Prox1 conditional mutant embryos, which have defective lymph sacs. However, subsequent clustering of hematopoietic cells within these developing lymph nodes is less efficient.

Key words: PROX1, Lymphatic endothelial cells, Lymphoid tissue inducer cell, Lymph nodes, Lymph sacs


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