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斑马鱼表达报告基因和突变体表明,免疫球蛋白超家族细胞粘附分子Dscamb是进食和生存所必需的。

Zebrafish expression reporters and mutants reveal that the IgSF cell adhesion molecule Dscamb is required for feeding and survival.

作者信息

Julien Donald P, Chan Alex W, Barrios Joshua, Mathiaparanam Jaffna, Douglass Adam, Wolman Marc A, Sagasti Alvaro

机构信息

a Department of Molecular, Cell and Developmental Biology and Molecular Biology Institute , University of California , Los Angeles , CA , USA.

b Department of Neurobiology and Anatomy , University of Utah , Salt Lake City , UT , USA.

出版信息

J Neurogenet. 2018 Dec;32(4):336-352. doi: 10.1080/01677063.2018.1493479. Epub 2018 Sep 11.

Abstract

Down syndrome cell adhesion molecules (DSCAMs) are broadly expressed in nervous systems and play conserved roles in programmed cell death, neuronal migration, axon guidance, neurite branching and spacing, and synaptic targeting. However, DSCAMs appear to have distinct functions in different vertebrate animals, and little is known about their functions outside the retina. We leveraged the genetic tractability and optical accessibility of larval zebrafish to investigate the expression and function of a DSCAM family member, dscamb. Using targeted genome editing to create transgenic reporters and loss-of-function mutant alleles, we discovered that dscamb is expressed broadly throughout the brain, spinal cord, and peripheral nervous system, but is not required for overall structural organization of the brain. Despite the absence of obvious anatomical defects, homozygous dscamb mutants were deficient in their ability to ingest food and rarely survived to adulthood. Thus, we have discovered a novel function for dscamb in feeding behavior. The mutant and transgenic lines generated in these studies will provide valuable tools for identifying the molecular and cellular bases of these behaviors.

摘要

唐氏综合征细胞粘附分子(DSCAMs)在神经系统中广泛表达,并在程序性细胞死亡、神经元迁移、轴突导向、神经突分支和间隔以及突触靶向中发挥保守作用。然而,DSCAMs在不同的脊椎动物中似乎具有不同的功能,并且人们对它们在视网膜外的功能知之甚少。我们利用斑马鱼幼体的遗传易处理性和光学可及性来研究DSCAM家族成员dscamb的表达和功能。通过靶向基因组编辑来创建转基因报告基因和功能丧失突变等位基因,我们发现dscamb在整个大脑、脊髓和外周神经系统中广泛表达,但对大脑的整体结构组织并非必需。尽管没有明显的解剖学缺陷,但纯合dscamb突变体摄取食物的能力不足,很少能存活到成年。因此,我们发现了dscamb在进食行为中的新功能。在这些研究中产生的突变体和转基因品系将为确定这些行为的分子和细胞基础提供有价值的工具。

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