Gap junctions – the channels that allow adjacent cells to exchange molecules – are made of two hemichannels that dock with one another through their extracellular domains. Undocked hemichannels are also thought to have roles in intercellular communication, but until now these had not been investigated in vivo. Gerald Kidder and colleagues () have been probing possible roles for undocked hemichannels, using mouse folliculogenesis as a model. During folliculogenesis, developing oocytes are surrounded and nurtured by granulosa cells that are connected to one another by gap junctions containing the protein connexin 43 (Cx43). To find out whether undocked hemichannels have a role in this process, the researchers produced constructs encoding wild-type Cx43 or a Cx43 mutant that can form hemichannels but not intercellular gap junctions. They then expressed these in Cx43-deficient granulosa cells and combined them with wild-type oocytes to make reaggregated ovaries. Whereas wild-type Cx43 constructs can rescue folliculogenesis, the mutant Cx43 construct cannot. So although in-vitro-based studies have shown evidence for gap-junction-independent roles, in this first in-vivo system undocked hemichannels cannot compensate for intercellular gap junctions.
