The roles of Pax6 in the development of the sensory system of the mammalian head

• Main Author: Parisi, Ida
• Published: University of Aberdeen 2011
• Subjects: 571.1; Mammals
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.558582

Although trigeminal ganglion morphogenesis has been intensively studied in birds, less is known about the molecular markers controlling mammalian cranial nerve development. A previously unsuspected role of the transcription factor Pax6 in regulating trigeminal neuronal precursor specification was investigated. Unlike in chick, Pax6 expression was observed in a subset of cells in the mouse developing trigeminal ganglion, overlapping both Pax3 expression, a specific marker of the ophthalmic placode (opV), and Islet1, the earliest neuronal marker for the maxillomandibular placode (mmV). The number of Islet1-positive cells at E9.5 in Pax6 mutants was significantly decreased, though the number of Pax3-positive cells was unaffected, suggesting a specific deficit in the specification of some of the sensory neuronal precursors. Analysis of nerve branching revealed abnormalities mainly within the maxillary division of the trigeminal nerve. In particular, Pax6 mutants have defects in the encirclement of the sensory axons around the whisker follicles, the major peripheral target of the maxillary branch. Neuropilin 1 expression was downregulated in the developing trigeminal ganglion in Pax6-null mutants. Furthermore we showed that perinatal expression of Pax6 is required for differentiation of Merkel cells, skin mechanoreceptors that in rodents represent the main peripheral target of the sensory free endings axons derived from the maxillary branch of the trigeminal nerve. Cytoplasmic localisation of Pax6 in developing Merkel cells was shown to be modulated by oxidative stress, as it is in the corneal epithelium. The data show that Pax6 has multiple roles at different levels of the whisker follicles somatosensory pathway controlling various aspects of this intensively studied neuronal circuit.