Published in

National Academy of Sciences, Proceedings of the National Academy of Sciences, 43(114), 2017

DOI: 10.1073/pnas.1707229114

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Modulation of apoptotic response by LAR family phosphatases–cIAP1 signaling during urinary tract morphogenesis

This paper is available in a repository.
This paper is available in a repository.

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Abstract

Significance Apoptotic morphogenesis requires strict regulation as both excessive and insufficient cell death is detrimental to tissue function. Here we use the process of ureter maturation, wherein the ureter connects to the bladder by the apoptosis-mediated removal of the intervening common nephric duct (CND), to investigate this paradigm. We find that LAR family phosphatases antagonize cIAP1 activity by decreasing its stability, thereby releasing the brake on CND elimination. In addition, we demonstrate that Birc2 (cIAP1) mutant embryos exhibit increased CND apoptosis, leading to accelerated ureter maturation and vesicoureteral reflux. Together this highlights the importance of modulating the rate of apoptosis during morphogenesis, which may act as a morphogenetic timer to allow for appropriate tissue rearrangements during embryonic development.