Epithelial tubular structure formation and maintenance are regulated by multiple factors such as cell proliferation, cell death, stem cell differentiation, and cell polarity. Recently the evolutionarily conserved Hippo signaling pathway was first identified as an important regulatory pathway for the cell proliferation, apoptosis, and organ size control in Drosophila. However, multiple homologues of each mammalian Hippo element exist, thus, the precise physiological functions of each Hippo element in mammals remain obscure. Moreover, homozygous null mutant mice lacking the component(s) of Hippo pathway such as NF2, MST1/2, WW45, or LATS2 are all early embryonic lethal, precluding study of these Hippo mediators both in tubulogenesis and tumorigenesis.

MOB1A and 1B are the adoptor proteins of LATS and NDR kinase. Within seven human MOB homologues, MOB1A is reported to be frequently down-regulated in human colorectal and non-small cell lung cancers, and deleted in melanoma and breast cell lines. However, the normal physiological function of MOB1 proteins in vivo is totally unknown. In this study, we will clarify the role of Mob1 in the epithelial tubular formation and its maintenance.

We will clarify the role of Mob1 in tubular formation and maintenance by generating and characterizing the Mob1A and Mob1B systemic double mutant mice. Moreover, because our preliminary experiments revealed that double homozygous mutant mice are early embryonic lethal, we will also generate the various tubular tissues-specific Mob1A and Mob1B double mutant mice.

Our study will clarify the role of Mob1 in the epithelial tubular formation, and may contribute to find the common mechanism on "Tubulogenesis". In addition, therapeutic strategies to control Mob1 expression (or Hippo signaling) might therefore benefit cancer patients, particularly those with tubular tissue-derived cancers.