Kirrel2 is differentially required in populations of olfactory sensory neurons for the targeting of axons in the olfactory bulb

Abstract

The formation of olfactory maps in the olfactory bulb (OB) is crucial for the control of innate and learned mouse behaviors. Olfactory sensory neurons (OSNs) expressing a specific odorant receptor project axons into spatially conserved glomeruli within the OB and synapse onto mitral cell dendrites. Combinatorial expression of members of the Kirrel family of cell adhesion molecules has been proposed to regulate OSN axonal coalescence; however, loss-of-function experiments have yet to establish their requirement in this process. We examined projections of several OSN populations in mice that lacked either Kirrel2 alone, or both Kirrel2 and Kirrel3. Our results show that Kirrel2 and Kirrel3 are dispensable for the coalescence of MOR1-3-expressing OSN axons to the most dorsal region (DI) of the OB. In contrast, loss of Kirrel2 caused MOR174-9-and M72-expressing OSN axons, projecting to the DII region, to target ectopic glomeruli. Our loss-of-function approach demonstrates that Kirrel2 is required for axonal coalescence in subsets of OSNs that project axons to the DII region and reveals that Kirrel2/3independent mechanisms also control OSN axonal coalescence in certain regions of the OB.

Synaptic Specificity, Recognition Molecules, and Assembly of Neural Circuits

“…These are also involved in synaptic specificity. For example, mouse Kirrels mediate synaptic selectivity of olfactory receptor axons in the olfactory bulb (Serizawa et al, 2006;Vaddadi et al, 2019), and Drosophila kirre mediates synapse formation in the fly visual system (Lü thy et al, 2014). Fly Dscams Pattern Synapses through Self-Avoidance and Dendritic Targeting There are four Dscam genes in Drosophila.…”

Establishment and Maintenance of Neural Circuit Architecture

“…In this new subcellular location, dbd formed functional synapses with the A08a lateral arbor, as Nose et al, 1997;Lee et al, 2001;Yamagata et al, 2002;Shen and Bargmann, 2003;Ango et al, 2004;Shen et al, 2004;Prakash et al, 2005;Dean and Dresbach, 2006;Serizawa et al, 2006;Chen and Clandinin, 2008;Kurusu et al, 2008;Yamagata and Sanes, 2008;Woo et al, 2009;DeNardo et al, 2012;Hong et al, 2012;Antinucci et al, 2013;Enneking et al, 2013;Mizumoto and Shen, 2013;Schwabe et al, 2013;Soto et al, 2013;Ashrafi et al, 2014;Duan et al, 2014;Kuwako et al, 2014;Lüthy et al, 2014;Krishnaswamy et al, 2015;Martin et al, 2015;Früh et al, 2016;Mountoufaris et al, 2017;X. Xie et al, 2017;Berns et al, 2018;Ashley et al, 2019;Cheng et al, 2019;Courgeon and Desplan, 2019;Menon et al, 2019;Tai et al, 2019;Vaddadi et al, 2019 Schuster et al, 1996;Dunah et al, 2005;Robbins et al, 2010;Zonta et al, 2011;Enneking et al, 2013;…”

Molecular and structural basis of olfactory sensory neuron axon coalescence by Kirrel receptors

“…Kirrels have been identified and implicated in numerous functional contexts in the nervous system. Loss of Kirrel2 and Kirrel3 causes disorganization of a subset of glomeruli in the main and accessory OBs ( Brignall et al, 2018 ; Nakashima et al, 2019 ; Prince et al, 2013 ; Vaddadi et al, 2019 ), and Kirrel3-knockout mice show behavioral abnormalities ( Hisaoka et al, 2018 ; Völker et al, 2018 ), including loss of male-male aggression likely as a result of miswiring in the AOB ( Prince et al, 2013 ). Furthermore, several Kirrel3 mutations in human autism and intellectual disability patients were identified (see Taylor et al, 2020 for a list).…”