Disorders of Axon Guidance

Variability in Neural Circuit Formation

“…(Other examples of human disorders arising from mutations in guidance or connectivity genes [including CNTNAP2, L1CAM, NTNG1, and PCDH19, for example] are reviewed in Engle 2010; Blockus and Chedotal 2015;Betancur and Mitchell 2015;and Yuasa-Kawada et al 2023. ) Most of these conditions are recessive, meaning both copies of the gene must be mutated to cause the phenotype (as is commonly observed for axon guidance genes in model organisms).…”

Transcriptional Control of Axon Guidance at Midline Structures

“…Intense research during the last few decades focused on how ipsilateral and contralateral axons behave at the midline in different species and contexts has lead to the identification of many families of cues, receptors, and signaling cascades involved in axon pathfinding. Post-transcriptional mechanisms such as the microRNA-dependent regulation of guidance receptors ( Yang et al, 2018 ), the regulation of local translation in axons ( Zhuang et al, 2019 ; Corradi and Baudet, 2020 ), the role of lipids in axon guidance ( Guy and Kamiguchi, 2021 ), novel ways of presenting guidance proteins ( Dominici et al, 2017 ; Moreno-Bravo et al, 2017 ; Varadarajan et al, 2017 ; Wu et al, 2019 ; Dorskind and Kolodkin, 2021 ), interactions between different families of receptors ( Zelina et al, 2014 ) or the targeted degradation of ligands or receptors ( Gorla et al, 2019 ), all contribute to guarantee proper axon guidance progression and today we know that aberrant expression of axon guidance proteins or alterations in any of these mechanisms may result in a wide variety of neurodevelopmental diseases ( Engle, 2010 ; Izzi and Charron, 2011 ; Nugent et al, 2012 ; Chédotal, 2014 ; Blockus and Chédotal, 2015 ; Van Battum et al, 2015 ; Roig-Puiggros et al, 2020 ). Despite these remarkable advances on the molecular mechanisms underlying axon guidance processes, current knowledge about the transcription factors (TFs) and the regulatory networks that orchestrate the expression of guidance molecules is still very limited ( Butler and Tear, 2007 ).…”