Spatially coordinated cell cycle activity and motility govern bifurcation of mammary branches

Author:

Myllymäki Satu-Marja1ORCID,Kaczyńska Beata1ORCID,Lan Qiang1ORCID,Mikkola Marja L.1ORCID

Affiliation:

1. Institute of Biotechnology, Helsinki Institute of Life Science, University of Helsinki 1 , Helsinki, Finland

Abstract

Branching morphogenesis is an evolutionary solution to maximize epithelial function in a compact organ. It involves successive rounds of branch elongation and branch point formation to generate a tubular network. In all organs, branch points can form by tip splitting, but it is unclear how tip cells coordinate elongation and branching. Here, we addressed these questions in the embryonic mammary gland. Live imaging revealed that tips advance by directional cell migration and elongation relies upon differential cell motility that feeds a retrograde flow of lagging cells into the trailing duct, supported by tip proliferation. Tip bifurcation involved localized repression of cell cycle and cell motility at the branch point. Cells in the nascent daughter tips remained proliferative but changed their direction to elongate new branches. We also report the fundamental importance of epithelial cell contractility for mammary branching morphogenesis. The co-localization of cell motility, non-muscle myosin II, and ERK activities at the tip front suggests coordination/cooperation between these functions.

Funder

Academy of Finland

Sigrid Jusélius Foundation

Jane and Aatos Erkko Foundation

Finnish Cancer Foundation

HiLIFE

Finnish Cultural Foundation

Publisher

Rockefeller University Press

Subject

Cell Biology

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