Expression of basement membrane type IV collagen chains during postnatal development in the murine cochlea

An immunofluorescence study was performed to examine the temporal and spatial patterns of expression for the different type IV collagen chains during postnatal cochlear development. At birth, the classical chains (4A1 and 4A2) were widely expressed, while the novel chains (4A3, 4A4, and 4A5) were completely absent. Activation of the novel chains was observed at 4 days of age, with intense, widely distributed immunostaining suggesting that most of the cells in the cochlea express the novel chains at this developmental stage. From day 8 through day 14, developmental inactivation of the novel chains results in a reduction of generalized immunoreactivity with a concomitant elevation of specific staining in the membranous structures bounding the interdental cells of the spiral limbus, the inner sulcus, the basilar membrane, and in a fibrous bed of staining radiating from the spiral prominence into the region of the spiral ligament which corresponds to the location of the root cell processes. This pattern of intense immunostaining for the novel chains persists through adulthood. The classical chains are expressed in these same anatomical regions only transiently (from day 6 to day 10), after which a gradual developmental inactivation leads to the adult expression pattern where classical collagen chains are found primarily in the perineurium, in the membranes surrounding the spiral ganglion cell bodies, and in the vascular basement membranes of the spiral ligament and the stria vascularis. The complex developmental pattern of expression for the type IV collagen chains in the murine cochlea is similar to that observed in the murine kidney, which is the other major site for basement membrane pathology in Alport syndrome.