A Novel Atoh1 “Self-Terminating” Mouse Model Reveals the Necessity of Proper Atoh1 Level and Duration for Hair Cell Differentiation and Viability
Figure 4
Some Myo7a-positive cells persist in adult Atoh1 CKO ears and display abnormal stereocilia.
(a–c’) In P21 control cochlea, one row of inner hair cells and three rows of outer hair cells are labeled by Myo7a (red) and the supporting cells are labeled by Tubulin (green). The pillar cells between the inner and outer hair cells are most strongly labeled. In the CKO cochlea, a few inner hair cells, which are medial to the strongly Tubulin-labeled pillar cells, can only be found at the apical tip (b, b’). The outer hair cells are reduced to one to two rows in the apex but become scattered in the middle turn and are surrounded or next to the remaining Tubulin-positive supporting cells. (d–g’) In contrast to the highly organized stereocilia found in all hair cells throughout the control cochlea, only few cells in the CKO cochlea are found to be hair cell-like, with stereocilia-like structures (e’, arrows in f, g). They are surrounded by, next to, or completely isolated from supporting cell-like cells. (h–i’) Immunohistochemistry of Myo7a and Tubulin shows hair cells and supporting cells in P38 ears. The control ear shows characteristic cellular distribution throughout the cochlea (h, h’). However, only a few Myo7a-positive cells remain in the CKO cochlea apex (i). The section shows that this hair cell is lateral to a Tubulin-labeled pillar cell-like cell and thus in the position of the first row of outer hair cells (i’). ‘[‘ and ‘{‘ in a and b indicate the location of inner and outer hair cells respectively. The dotted lines in h and i indicate the approximate position of the sections shown in h’ and i’. 1, 2, 3, three rows of outer hair cells; IHC, inner hair cells; IPC, inner pillar cell, OPC; outer pillar cell; PC, pillar cells. Bar indicates 100 µm in a–b’, h, 10 µm in c, c’, d, e, h’, i, i’, and 1 µm in d’ e’, f, g.