2012 Fiscal Year Final Research Report

Roles of novel genes encoding secreted proteins in morphogenesis

Research Project

Project/Area Number	23659035
Research Category	Grant-in-Aid for Challenging Exploratory Research
Allocation Type	Multi-year Fund
Research Field	Biological pharmacy
Research Institution	Kyoto University
Principal Investigator	ITOH Nobuyuki 京都大学, 大学院・薬学研究科, 教授 (10110610)
Co-Investigator(Renkei-kenkyūsha)	MIYAKE Ayumi 京都大学, 大学院・薬学研究科, 講師 (40346044)
Project Period (FY)	2011 – 2012
Keywords	分子物学
Research Abstract	We identified a gene encoding a novel secreted protein in mice, humans, and zebrafish including Brorin, Brorin-like, Neucrin, and Fgf22. The inhibition of Brorin and Brorin-like functions in zebrafish resulted in the impairment of neural development. Brorin-like potentially plays roles in neural development and functions. The knockdown of neucrin also suppressed neuronal differentiation and caused increased cell proliferation and apoptosis in developing neural tissues. Neucrin plays roles in neural development in zebrafish. The Fgf22 morphants were defective in proper formation of the MHB constriction and the midbrain. The knockdown of Fgf22 caused decreased cell proliferation in the midbrain, expanded expression of roof plate and tegmental marker genes, and decreased expression of tectal marker genes. Furthermore, Fgf22 partially rescued the Fgf3/fgf8 double morphant phenotype. Fgf22 is involved in midbrain development downstream of Fgf3 and Fgf8 in the MHB but not of Hh in the floor plate.