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. 2022 Apr 28;16:889155. doi: 10.3389/fnins.2022.889155

FIGURE 2.

FIGURE 2

Adhesive functions of CAMs in circuit wiring. (A) Integrins mediate adhesion to the ECM for growth cone advance. Binding of integrins to ECM ligands leads to the clustering of integrins and the recruitment of adaptor proteins linking integrins to the actin cytoskeleton. The point contacts hence formed promote growth cone advance by stabilizing filopodial protrusions and restraining the retrograde flow of actin at the growth cone periphery. (B) Integrins mediate adhesion to the ECM for target selection. In the visual system, integrin α8β1 is selectively expressed by retinal ganglion cells projecting ipsilaterally. Its ligand, the ECM glycoprotein Nephronectin, is restricted to a sublamina at the target. Interaction between integrin α8β1 and Nephronectin is necessary for the laminar targeting of ipsilateral axons to the rostral stratum opticum (SO). Deleting integrin α8β1 or Nephronectin causes a dramatic loss of ipsilateral projections while contralateral projections remain unaffected in the stratum griseum superficial (SGS). Adapted from Su et al. (2021). (C,D) Protocadherin-17 (Pcdh17) mediates trans-axonal interactions for proper tract formation. (C) Pcdh17 accumulates at homotypic contacts between growth cones and axons from amygdala neurons, where it recruits the WAVE complex, Lamellipodin, and Ena/VASP proteins that remodel the actin cytoskeleton and promote membrane protrusion. Pcdh17-mediated adhesion enhances growth cone motility and enable growth cone advance along homotypic axons. (D) Pcdh17 is required for the extension of amygdala axons through the stria terminalis toward the hypothalamus. Adapted from Hayashi et al. (2014). (E) A CAM code specifies laminar targeting and synaptic specificity in the retina. Sdk1, Sdk2, Dscam, DscamL, and Cntns (not all a represented here) are expressed in non-overlapping subsets of bipolar (green), amacrine (orange), and retinal ganglion cells (purple) and engage in homophilic trans-interactions to direct synapse formation between matching partners in specific laminae (S1–S5) of the inner plexiform layer (IPL). Classical cadherins (Cdh) also contribute to the molecular code specifying connections. INL, inner nuclear layer; GCL, ganglion cell layer. Adapted from Sanes and Zipursky (2020).