Roles of DSCAM in axonal decussation and fasciculation of chick spinal interneurons

Cohen, Oksana; Vald, Lilach; Yamagata, Masahito; Sanes, Joshua R.; Klar, Avihu

doi:10.1387/ijdb.160235ak

Cited by 7 publications

(8 citation statements)

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“…In retinal ganglion cells (RGCs), DSCAM downregulation leads to reduced axon extension and complexity levels in Xenopus (Santos et al, 2018), and delayed optic nerve outgrowth and thalamic targeting, accompanied by axonal fasciculation impairments, in mice (Bruce et al, 2017). Likewise, chick spinal cord interneurons present reduced axonal fasciculation levels upon DSCAM knockdown (Cohen et al, 2017). On the other hand, DSCAM knockout in Xenopus tectal neurons in vivo is associated with increased dendritic growth and branching rates.…”

Section: Discussionmentioning

confidence: 99%

Subtle Roles of Down Syndrome Cell Adhesion Molecules in Embryonic Forebrain Development and Neuronal Migration

Mitsogiannis

Pancho

Aerts

et al. 2021

Front. Cell Dev. Biol.

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Down Syndrome (DS) Cell Adhesion Molecules (DSCAMs) are transmembrane proteins of the immunoglobulin superfamily. Human DSCAM is located within the DS critical region of chromosome 21 (duplicated in Down Syndrome patients), and mutations or copy-number variations of this gene have also been associated to Fragile X syndrome, intellectual disability, autism, and bipolar disorder. The DSCAM paralogue DSCAM-like 1 (DSCAML1) maps to chromosome 11q23, implicated in the development of Jacobsen and Tourette syndromes. Additionally, a spontaneous mouse DSCAM deletion leads to motor coordination defects and seizures. Previous research has revealed roles for DSCAMs in several neurodevelopmental processes, including synaptogenesis, dendritic self-avoidance, cell sorting, axon growth and branching. However, their functions in embryonic mammalian forebrain development have yet to be completely elucidated. In this study, we revealed highly dynamic spatiotemporal patterns of Dscam and Dscaml1 expression in definite cortical layers of the embryonic mouse brain, as well as in structures and ganglionic eminence-derived neural populations within the embryonic subpallium. However, an in-depth histological analysis of cortical development, ventral forebrain morphogenesis, cortical interneuron migration, and cortical-subcortical connectivity formation processes in Dscam and Dscaml1 knockout mice (Dscamdel17 and Dscaml1GT) at several embryonic stages indicated that constitutive loss of Dscam and Dscaml1 does not affect these developmental events in a significant manner. Given that several Dscam- and Dscaml1-linked neurodevelopmental disorders are associated to chromosomal region duplication events, we furthermore sought to examine the neurodevelopmental effects of Dscam and Dscaml1 gain of function (GOF). In vitro, ex vivo, and in vivo GOF negatively impacted neural migration processes important to cortical development, and affected the morphology of maturing neurons. Overall, these findings contribute to existing knowledge on the molecular etiology of human neurodevelopmental disorders by elucidating how dosage variations of genes encoding adhesive cues can disrupt cell-cell or cell-environment interactions crucial for neuronal migration.

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Section: Discussionmentioning

confidence: 99%

Subtle Roles of Down Syndrome Cell Adhesion Molecules in Embryonic Forebrain Development and Neuronal Migration

Mitsogiannis

Pancho

Aerts

et al. 2021

Front. Cell Dev. Biol.

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“…It mediates homophilic attraction in neuronal layer-targeting [ 15 ]. Recently DSCAM has been identified as another receptor for netrin-1 [ 16 ]. It also works as a receptor for netrin in mediating axon guidance [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

Association between DSCAM polymorphisms and non-syndromic Hirschsprung disease in Chinese population

Wang

Zhang

et al. 2018

BMC Med Genet

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BackgroundHirschsprung disease (HSCR, aganglionic megacolon) is the most frequent genetic cause of congenital intestinal obstruction. DSCAM was identified as associated to HSCR with Down Syndrome (DS-HSCR) in European population,but failed to replicate in the non-syndromic HSCR patients. We aim to further investigate the relationship of DSCAM with non-sydromic HSCR in a South Chinese cohort, the largest case-control study so far.MethodWe analyzed 1394 HSCR patients and 973 healthy controls. Two polymorphisms (rs2837770 A > G, rs8134673 A > G) on DSCAM were genotyped using Sequenom Massarray platform.ResultsBoth SNPs were confirmed as associated with non-syndromic HSCR in the South Chinese population (P = 1.69E-03, OR = 1.29 for SNP rs2837770 and P = 3.00E-03, OR = 1.27 for SNP rs8134637). Of note, we demonstrated the associated SNPs were more likely to affect a subgroup of patients with short-segment aganglionosis (S-HSCR) (P = 3.06E-03,OR = 1.21 for SNP rs2837770 and P = 3.33E-03,OR = 1.21 for SNP rs8134637).ConclusionThere is an association between DSCAM polymorphisms and non-syndromic HSCR in South Chinese population.Electronic supplementary materialThe online version of this article (10.1186/s12881-018-0637-2) contains supplementary material, which is available to authorized users.

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“…Possibly independently of either UNC5 or DCC, DSCAM interacts with AMP-activated protein kinase (AMPK), which is phosphorylated in response to netrin-1 treatment ( Zhu et al, 2013 ). DSCAM promotes axonal fasciculation and dendritic tiling through neurite-neurite adhesion ( Millard and Zipursky, 2008 ; Tadros et al, 2016 ; Cohen et al, 2017 ). Further studies are required to mechanistically define how DSCAM mediates diverse functions during netrin-1 dependent morphogenesis.…”

Section: Netrin-1 Receptors and Their Mechanismsmentioning

confidence: 99%

Revisiting Netrin-1: One Who Guides (Axons)

Boyer¹,

Gupton²

2018

Front. Cell. Neurosci.

136

130

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Proper patterning of the nervous system requires that developing axons find appropriate postsynaptic partners; this entails microns to meters of extension through an extracellular milieu exhibiting a wide range of mechanical and chemical properties. Thus, the elaborate networks of fiber tracts and non-fasciculated axons evident in mature organisms are formed via complex pathfinding. The macroscopic structures of axon projections are highly stereotyped across members of the same species, indicating precise mechanisms guide their formation. The developing axon exhibits directionally biased growth toward or away from external guidance cues. One of the most studied guidance cues is netrin-1, however, its presentation in vivo remains debated. Guidance cues can be secreted to form soluble or chemotactic gradients or presented bound to cells or the extracellular matrix to form haptotactic gradients. The growth cone, a highly specialized dynamic structure at the end of the extending axon, detects these guidance cues via transmembrane receptors, such as the netrin-1 receptors deleted in colorectal cancer (DCC) and UNC5. These receptors orchestrate remodeling of the cytoskeleton and cell membrane through both chemical and mechanotransductive pathways, which result in traction forces generated by the cytoskeleton against the extracellular environment and translocation of the growth cone. Through intracellular signaling responses, netrin-1 can trigger either attraction or repulsion of the axon. Here we review the mechanisms by which the classical guidance cue netrin-1 regulates intracellular effectors to respond to the extracellular environment in the context of axon guidance during development of the central nervous system and discuss recent findings that demonstrate the critical importance of mechanical forces in this process.

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Roles of DSCAM in axonal decussation and fasciculation of chick spinal interneurons

Cited by 7 publications

References 0 publications

Subtle Roles of Down Syndrome Cell Adhesion Molecules in Embryonic Forebrain Development and Neuronal Migration

Subtle Roles of Down Syndrome Cell Adhesion Molecules in Embryonic Forebrain Development and Neuronal Migration

Association between DSCAM polymorphisms and non-syndromic Hirschsprung disease in Chinese population

Revisiting Netrin-1: One Who Guides (Axons)

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