Cadherin‐2 function in the cranial ganglia and lateral line system of developing zebrafish

Abstract

Cadherins are cell surface molecules that mediate cell-cell adhesion through homophilic interactions. Cadherin-2 (also called N-cadherin), a member of classic cadherin subfamily, has been shown to play important roles in development of a variety of tissues and organs, including the nervous system. We recently reported that cadherin-2 was strongly expressed by the majority of cranial ganglia and lateral line system of developing zebrafish. To gain insight into cadherin-2 role in the formation of these structures, we have used several markers to analyze zebrafish embryos injected with a specific cadherin-2 antisense morpholino oligonucleotide (cdh2MO). We find that development of several cranial ganglia, including the trigeminal, facial, and vagal ganglia, and the lateral line ganglia and neuromasts of the cdh2MO-injected embryos are severely disrupted. These phenotypes were confirmed by analyzing a cadherin-2 mutant, glass onion. Our results suggest that cadherin-2 function is crucial for the normal formation of the zebrafish lateral line system and a subset of cranial ganglia.

Cadherin‐4 plays a role in the development of zebrafish cranial ganglia and lateral line system

“…This was not surprising since cdh4 expression is detected in the gVIII of slightly younger embryos (26 hpf), and not observed in other ganglia until 32 hpf (Liu et al, 2003). In contrast, disruption of cadherin2 expression (expressed throughout the development of most of the cranial and lateral line ganglia; Liu et al, 2003) in developing zebrafish resulted in detectable abnormalities in these ganglia as early as 25 hpf (Kerstetter et al, 2004). However, by 50 -55 hpf, development of the ganglia was disrupted in the vast majority of cdh4 morphants (Table 1).…”

“…Morpholino antisense oligonucleotide techniques have been successfully employed in zebrafish to study gene function in various tissues and organs including the cranial and/or lateral line system (Ekker, 2000;Nasevicius and Ekker, 2000;Andermann et al, 2002;Kerstetter et al, 2004;Knaut et al, 2005). Injection of cdh4-specific antisense morpholino oligonucleotides (cdh4 MOs: RcadMphA, 0.25 mM, 2.1 ng/embryo, or RcadMphB, 0.12 mM, 1.0 ng/embryo), into one-to four-cell stage zebrafish embryos greatly reduced Cdh4 protein levels in the injected embryos at 50 -55 hpf ( Fig.…”

“…In cadherin2 morphants or in a cadherin2 mutant glass onion, the gV/AD and their nerve defects are much more severe, with highly fragmented ganglia, defasciculated, missing, or unrecognizable nerves (Kerstetter et al, 2004), compared to cdh4 morphants. On the other hand, the severity of gX defects in cdh4 morphants, cadherin2 morphants, and glass onion mutants is similar.…”

“…The nP defect in the morphants correlates well with Cdh4/cdh4 expression in the system (Liu et al, 2003), suggesting that Cdh4 is involved in the extension of the nerve. Moreover, the nP defects in the cdh4 morphants are different from those of embryos with disrupted cadherin-2 function, in which the nP had greatly altered trajectories (curved or turned around), instead of reduced length (Kerstetter et al, 2004). The growth cones of nP in developing zebrafish are always found to be associated with the primordium of the posterior lateral line (PLLp) (Metcalfe, 1989), and pathfinding of the nP depends on the migrating PLLp (Gilmour et al, 2004).…”

“…Transcription factors neurogenin, foxd3 and NeuroD (Fode et al, 1998;Ma et al, 1998;Kim et al, 2001;Andermann et al, 2002), chemokine guidance receptor Cxcr4b (Knaut et al, 2005;Haas and Gilmour, 2006), and cell adhesion molecule cadherin-2 (Kerstetter et al, 2004) have been implicated in the development of the cranial ganglia and/or lateral line system.…”