Distinct roles for the cell adhesion molecule Contactin2 in the development and function of neural circuits in zebrafish

Abstract

Contactin2 (Cntn2)/Transient Axonal Glycoprotein 1 (Tag1), a neural cell adhesion molecule, has established roles in neuronal migration and axon fasciculation in chick and mouse. In zebrafish, antisense morpholino-based studies have indicated roles for cntn2 in the migration of facial branchiomotor (FBM) neurons, the guidance of the axons of the nucleus of the medial longitudinal fascicle (nucMLF), and the outgrowth of Rohon-Beard (RB) central axons. To study functions of Cntn2 in later stages of neuronal development, we generated cntn2 mutant zebrafish using CRISPR-Cas9. Using a null mutant allele, we detected genetic interactions between cntn2 and the planar cell polarity gene vangl2, as shown previously with cntn2 morphants, demonstrating a function for cntn2 during FBM neuron migration in a sensitized background of reduced planar cell polarity signaling. In addition, maternal-zygotic (MZ) cntn2 mutant larvae exhibited aberrant touch responses and swimming, suggestive of defects in sensorimotor circuits, consistent with studies in mice. However, the nucMLF axon convergence, FBM neuron migration, and RB outgrowth defects seen in morphants were not seen in the mutants, and we show here that they are likely off-target effects of morpholinos. However, MLF axons exhibited local defasciculation in MZcntn2 mutants, consistent with a role for Cntn2 in axon fasciculation. These data demonstrate distinct roles for zebrafish cntn2 in neuronal migration and axon fasciculation, and in the function of sensorimotor circuits.

TAG-1 Multifunctionality Coordinates Neuronal Migration, Axon Guidance, and Fasciculation

“…Previously, TAG-1 has been implicated in facilitating facial MN migration in the zebrafish hindbrain (Gurung et al, 2018). This contrasts with our finding that TAG-1 restricts, rather than promotes, migration and aberrant spinal cord exit of MNs in the mouse hindbrain.…”

Acetaminophen Disrupts the Development of Pharyngeal Arch-Derived Cartilage and Muscle in Zebrafish

“…Using 3.9-mM APAP, we found no significant difference in hatching behavior ( Figure S1 ) when meticulously cared for to ensure high survivability. We also probed for sensorimotor defects using a touch response assay [ 27 ] and observed that despite normal hatching behavior, APAP-treated embryos were substantially less responsive to head or tail touches ( Figure S2 ). And despite virtually no death within the first several days, APAP-treated embryos showed reduced heart rates from 1–3 dpf ( Figure S3 ).…”

“…The touch response assay was performed as previously described [ 27 ]. Each 2-dpf embryo was placed into a glass dish and aligned to the center of a 20-mm field of view under a stereo microscope.…”

High-throughput transcriptome sequencing reveals the key stages of cardiovascular development in zebrafish embryos

“…These results are consistent with those of previous studies [ 21 ]. Other research has reported that cntn2 is involved in branchiomotor neuron migration [ 22 – 24 ], spinal cord regeneration [ 25 ], and axon fasciculation [ 26 ]. Nevertheless, the role of cntn2 in intersegmental blood vessels has yet not been reported.…”