ERK and MMPs sequentially regulate distinct stages of epithelial tubule development - PubMed (original) (raw)
ERK and MMPs sequentially regulate distinct stages of epithelial tubule development
Lucy Erin O'Brien et al. Dev Cell. 2004 Jul.
Free article
Abstract
Epithelial cells undergo tubulogenesis in response to morphogens such as hepatocyte growth factor (HGF). To organize into tubules, cells must execute a complex series of morphogenetic events; however, the mechanisms that underlie the timing and sequence of these events are poorly understood. Here, we show that downstream effectors of HGF coordinately regulate successive stages of tubulogenesis. Activation of extracellular-regulated kinase (ERK) is necessary and sufficient for the initial stage, during which cells depolarize and migrate. ERK becomes dispensable for the latter stage, during which cells repolarize and differentiate. Conversely, the activity of matrix metalloproteases (MMPs) is essential for the late stage but not the initial stage. Thus, ERK and MMPs define two regulatory subprograms that act in sequence. By inducing these reciprocal signals, HGF directs the morphogenetic progression of tubule development.
Comment in
- Making tubes: step by step.
Rosário M, Birchmeier W. Rosário M, et al. Dev Cell. 2004 Jul;7(1):3-5. doi: 10.1016/j.devcel.2004.06.015. Dev Cell. 2004. PMID: 15239947 Review.
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