Abnormal cochlear connectivity in <i>Hoxb1</i>, <i>Hoxb2</i> and <i>Hoxa2</i> mutants.

<p>(A) Oblique P8 coronal sections show abnormal presence of YFP⁺ fibers projecting to the medial nuclei of the trapezoid body (MNTB) in <i>Hoxb1^null</i> and <i>Hoxb1^lateCKO</i> mutants. Right panels: enlarged views of the boxed areas to the left depicting abnormal YFP⁺ terminals (arrowheads) of labeled crossed fibers (arrows) surrounding cells of the MNTB (limited by solid line). (B) Schematic representation showing the position of the injected dextran at the level of the PVCN (asterisk). Normally, PVCN interneurons innervate contralateral MOC neurons, as indicated in the control coronal section (arrow). In <i>Hoxb2^ΔKO</i> mutants, projections originating from the PVCN target now AVCN-specific targets, such as the contralateral MNTB (cMNTB) (arrowhead) and the lateral superior olivary (LSO) nuclei. (C) Schematics summarizing the normal connectivity pattern of cochlear AVCN neurons towards the nuclei of the superior olivary complex (SOC) complex, and the abnormal presence of YFP⁺ neurons behaving like AVCN neurons when <i>Hoxb1</i> or <i>Hoxb2</i> are inactivated. (D) A subpopulation of AVCN-labeled axons project abnormally to the ipsilateral MNTB (see arrowhead) when <i>Hoxa2</i> is conditionally inactivated in the <i>Wnt1⁺</i> (rhombic lip) domain. Expression of the Slit receptor <i>Rig1</i> (or <i>Robo3</i>) is decreased in the VCN, indicating that absence of <i>Rig1</i> affects midline crossing of AVCN projections. (E) Schematics summarizing the abnormal axonal projections of AVCN neurons in <i>Wnt::Cre;Hoxa2lox/lox</i> mice after dextran injection in the AVCN. AVCN, anterior ventral cochlear nucleus; PVCN, posterior ventral cochlear nucleus; PVCN IN, PVCN interneurons; MOC, medial olivocochlear neurons; aes, anterior extramural stream. Scale bars: 400 µm (A left panels, B), 50 µm (A right panels).