RT Journal Article SR Electronic T1 Cbln1 regulates axon growth and guidance in multiple neural regions JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.11.16.468844 DO 10.1101/2021.11.16.468844 A1 Peng Han A1 Yuanchu She A1 Zhuoxuan Yang A1 Mengru Zhuang A1 Qingjun Wang A1 Xiaopeng Luo A1 Chaoqun Yin A1 Junda Zhu A1 Samie R. Jaffrey A1 Sheng-Jian Ji YR 2021 UL http://biorxiv.org/content/early/2021/11/16/2021.11.16.468844.abstract AB The accurate construction of neural circuits requires the precise control of axon growth and guidance, which is regulated by multiple growth and guidance cues during early nervous system development. It is generally thought that the growth and guidance cues that control the major steps of axon guidance have been defined. Here, we describe cerebellin-1 (Cbln1) as a novel cue that controls diverse aspects of axon growth and guidance throughout the central nervous system (CNS). Cbln1 has previously been shown to function in late neural development to influence synapse organization. Here we find that Cbln1 has an essential role in early neural development. Cbln1 is expressed on the axons and growth cones of developing commissural neurons and functions in an autocrine manner to promote axon growth. Cbln1 is also expressed in intermediate target tissues and functions as an attractive guidance cue. We find that these functions of Cbln1 are mediated by neurexin-2 (Nrxn2), which functions as the Cbln1 receptor for axon growth and guidance. In addition to the developing spinal cord, we further show that Cbln1 functions in diverse parts of the CNS with major roles in cerebellar parallel fiber growth and retinal ganglion cell axon guidance. Despite the prevailing role of Cbln1 as a synaptic organizer, our study discovers a new and unexpected function for Cbln1 as a general axon growth and guidance cue throughout the nervous system.Impact statement Despite the prevailing role of Cbln1 as a synaptic organizer, our study discovers a new and unexpected function for Cbln1 as a general axon growth and guidance cue throughout the nervous system.Competing Interest StatementThe authors have declared no competing interest.